Affinage

GLO1

Lactoylglutathione lyase · UniProt Q04760

Length
184 aa
Mass
20.8 kDa
Annotated
2026-04-28
73 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLO1 encodes glyoxalase 1, a glutathione-dependent enzyme that catalyzes the detoxification of methylglyoxal (MG), a reactive dicarbonyl byproduct of glycolysis, thereby preventing MG-driven protein and DNA glycation (AGE formation) and maintaining genome integrity (PMID:20544845, PMID:29385725). GLO1 expression is transcriptionally regulated by NF-κB downstream of Ras/ERK and PI3K/Akt signaling, by MMSET I binding at its promoter, by YBX1 recruited via noncoding RNAs, and by the JAK2/STAT3/Nrf2 axis, while its enzymatic activity is post-translationally modulated by crotonylation at K157 (inhibitory, reversed by HDAC1/HDAC3) and by itaconate-driven proteasomal degradation via Cys139 alkylation (PMID:25569448, PMID:30470837, PMID:36576700, PMID:40138913, PMID:39787788). In the nervous system, neuronal GLO1 controls anxiety-like behavior by regulating MG levels in the basolateral amygdala and maintains the cortical neural precursor pool during embryonic development (PMID:26711908, PMID:27760310). In cancer, GLO1 sustains malignant cell survival under glycolytic and hypoxic stress, supports glioma stem cell maintenance through Sox2-dependent transcriptional programs, and promotes metastasis by stabilizing glutathione synthetase (GSS) to preserve redox homeostasis (PMID:20544845, PMID:42011505, PMID:40492378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2010 High

    Establishing GLO1 as a functional methylglyoxal detoxification enzyme required for cancer cell survival resolved the question of whether GLO1 is merely a metabolic housekeeping gene or an actionable survival factor under glycolytic stress.

    Evidence siRNA knockdown and pharmacological inhibition with BBGC across multiple cancer cell lines with apoptosis readout

    PMID:20544845

    Open questions at the time
    • Catalytic mechanism not structurally resolved in this study
    • Relative contribution of GLO1 vs. GLO2 to MG clearance not addressed
    • In vivo tumor dependency not tested
  2. 2010 Medium

    Identifying Hsp27 as a major MG-adducted protein upon GLO1 loss revealed a specific downstream target of unchecked methylglyoxal toxicity.

    Evidence 2D proteomics and mass spectrometry of anti-argpyrimidine-reactive proteins in GLO1-knockdown melanoma cells

    PMID:20093988

    Open questions at the time
    • Only one adducted substrate identified; global adductome not mapped
    • Functional consequence of Hsp27 glycation not determined
    • Single cell line
  3. 2013 Medium

    Demonstrating that GLO1 knockdown increases surface GLUT4 via reduced internalization under hyperglycemia linked GLO1-MG metabolism to glucose transporter trafficking, extending its role beyond detoxification to metabolic regulation.

    Evidence siRNA knockdown in L6 myoblasts with myc-tagged GLUT4 surface assay and NAC rescue

    PMID:23717693

    Open questions at the time
    • Direct MG target mediating GLUT4 retention unknown
    • Not replicated in primary muscle cells or in vivo
    • Mechanism of endocytosis inhibition by MG not resolved
  4. 2014 Medium

    The Ala111 coding variant (C332) was shown to reduce GLO1 enzymatic activity without altering protein levels and to correlate with increased AGE formation in human tissues, establishing a genotype–activity–glycation axis relevant to human disease.

    Evidence Enzymatic activity assays in human leukocytes and post-mortem brain, genotype-stratified AGE quantification

    PMID:25201284

    Open questions at the time
    • Structural basis for reduced activity not determined
    • Causal link to specific neuropsychiatric or metabolic disease not established in this study
    • Single cohort
  5. 2014 Medium

    Observation that GLO1 undergoes MEK/ERK-dependent nuclear translocation in aggressive tumor cells raised the possibility of non-cytosolic functions beyond canonical MG detoxification.

    Evidence Subcellular fractionation, immunofluorescence, MEK inhibitor (U0126) treatment in murine fibrosarcoma lines

    PMID:24532130

    Open questions at the time
    • Nuclear function of GLO1 undefined
    • No nuclear substrate or binding partner identified
    • Mechanism of translocation not resolved
  6. 2015 Medium

    Mapping GLO1 expression downstream of Ras/ERK and Ras/PI3K/Akt via NF-κB placed GLO1 transcription under oncogenic signaling control, explaining its frequent upregulation in cancer.

    Evidence Pathway-specific inhibitors (U0126, LY294002, JSH-23) in AML cells with GLO1 expression readout

    PMID:25569448

    Open questions at the time
    • Direct NF-κB binding to GLO1 promoter not shown by ChIP
    • Contribution of other transcription factors not excluded
    • Single cell line
  7. 2015 High

    Neuronal-specific Glo1 overexpression and direct amygdala MG injection demonstrated that GLO1 modulates anxiety-like behavior through MG levels in the basolateral amygdala, establishing a neuroactive role for a metabolic enzyme.

    Evidence Conditional transgenic Glo1 overexpression (ROSA26 × Syn-Cre), stereotaxic MG microinjection, elevated plus maze and open field tests

    PMID:26711908

    Open questions at the time
    • Molecular target of MG in neurons (e.g., GABA-A receptor modulation) not directly shown in this study
    • Chronic vs. acute MG effects not distinguished
    • Human relevance of GLO1-anxiety link not established
  8. 2016 High

    Glo1 loss-of-function in embryonic neural precursor cells caused premature neurogenesis and NPC depletion, extending GLO1's biological role to neural stem cell pool maintenance during cortical development.

    Evidence Glo1 knockdown in embryonic cortical NPCs and maternal MG exposure model with postnatal cortical neuron analysis

    PMID:27760310

    Open questions at the time
    • Downstream MG target driving premature differentiation not identified
    • Whether effect is MG-dose-dependent or threshold-based unknown
    • Long-term behavioral consequence of NPC depletion not tested
  9. 2018 High

    GLO1 inhibition in glioblastoma cells increased the DNA-AGE CEdG and RAGE expression, triggering apoptosis, which demonstrated that GLO1 protects tumor cells from MG-induced DNA glycation and the consequent RAGE-mediated death cascade.

    Evidence Pharmacological and shRNA GLO1 inhibition in GBM cells and orthotopic xenografts with CEdG and RAGE quantification

    PMID:29385725

    Open questions at the time
    • Whether CEdG is the causative lesion or a biomarker not resolved
    • RAGE-independent apoptotic contributions not excluded
    • DNA repair response to CEdG not characterized
  10. 2018 High

    ChIP-qPCR showing MMSET I binding upstream of GLO1 and functional rescue by GLO1 overexpression identified GLO1 as a direct transcriptional target and effector of MMSET I in myeloma.

    Evidence ChIP-qPCR at GLO1 locus, MMSET I knockdown with GLO1 overexpression rescue in KMS11 myeloma cells

    PMID:30470837

    Open questions at the time
    • Whether MMSET I histone methylation activity is required for GLO1 induction not tested
    • Contribution of other MMSET I targets to the phenotype not excluded
  11. 2019 High

    Bidirectional manipulation of GLO1 in vascular smooth muscle cells revealed it as a negative regulator of angiotensin II–driven proliferation via PI3K/AKT/CDK2, and AAV-mediated Glo1 overexpression ameliorated cerebrovascular remodeling in hypertensive mice.

    Evidence GLO1 knockdown/overexpression in BASMCs, signaling analysis, AAV delivery in hypertensive mouse model

    PMID:31420161

    Open questions at the time
    • Whether MG directly activates PI3K or acts via AGE/RAGE not resolved
    • Specificity to vascular vs. other smooth muscle not tested
  12. 2020 High

    CRISPR knockout of GLO1 in melanoma identified TXNIP as the most upregulated gene and showed broad metabolic reprogramming (GLUT1, LDHA, hexosamine pathway), establishing GLO1 as a regulator of metabolic gene networks via MG.

    Evidence CRISPR/Cas9 GLO1 KO in A375 cells, NanoString profiling, metabolite analysis, pharmacological MG mimicry

    PMID:33360689

    Open questions at the time
    • Mechanism linking MG to TXNIP transcriptional induction not defined
    • Immune checkpoint (PDL1) regulation not causally dissected
    • In vivo consequence of TXNIP upregulation not tested
  13. 2022 Medium

    Identification of YBX1 as a GLO1 promoter-binding transcription factor recruited by lncRNA RP11-162G10.5 established a noncoding RNA–transcription factor axis controlling GLO1 expression in breast cancer.

    Evidence ChIP, luciferase reporter, knockdown/rescue experiments, xenograft validation

    PMID:36576700

    Open questions at the time
    • Whether YBX1 is sufficient without the lncRNA not tested
    • Broader applicability beyond breast cancer not established
  14. 2024 Medium

    Placing GLO1 downstream of the JAK2/STAT3/Nrf2 pathway in castration-resistant prostate cancer provided an additional transcriptional regulatory axis and showed GLO1 as a survival effector in therapy-resistant contexts.

    Evidence Butyrate treatment, STAT3 activator rescue, GLO1 overexpression rescue in DU145 cells

    PMID:38577936

    Open questions at the time
    • Direct Nrf2 binding to GLO1 promoter not confirmed by ChIP
    • Single cell line
    • In vivo relevance not tested
  15. 2024 Medium

    SIRT2 and NAMPT knockdown reduced GLO1 protein and activity without altering GLO1 acetylation, revealing NAD+-dependent but acetylation-independent regulation of GLO1 in muscle cells.

    Evidence siRNA knockdown of SIRT2 and NAMPT in human myotubes, GLO1 activity assays, acetylation immunoprecipitation

    PMID:39142179

    Open questions at the time
    • Mechanism by which NAD+ supports GLO1 expression/stability undefined
    • Whether SIRT2 acts transcriptionally or post-translationally unclear
    • Single tissue type
  16. 2025 High

    Itaconate was shown to alkylate GLO1 at Cys139 and trigger its proteasomal degradation in macrophages, linking innate immune metabolite signaling to methylglyoxal accumulation and AGE/RAGE-driven inflammation in sepsis.

    Evidence Site-directed mutagenesis of Cys139, proteasomal degradation assays, patient PBMC analysis, myeloid-specific AGER knockout mice in sepsis model

    PMID:39787788

    Open questions at the time
    • E3 ubiquitin ligase mediating degradation not identified
    • Whether other cysteine modifications similarly destabilize GLO1 not tested
    • Therapeutic potential of blocking Cys139 alkylation not explored
  17. 2025 High

    Discovery that crotonylation at K157 inhibits GLO1 enzymatic activity, reversed by HDAC1/HDAC3, identified a new post-translational regulatory switch relevant to vascular oxidative stress.

    Evidence PTM proteomics, site-directed mutagenesis in HEK293 cells, HDAC overexpression, ex vivo ITA/SV tissue analysis

    PMID:40138913

    Open questions at the time
    • Acetyltransferase responsible for K157 crotonylation not definitively identified beyond CBP correlation
    • In vivo vascular outcome of K157 mutation not tested
    • Interplay between K157 crotonylation and Cys139 itaconation unknown
  18. 2025 Medium

    NRF2-dependent upregulation of GLO1 in TXNIP-deficient patient cells established a feedback loop where increased glycolytic flux activates NRF2 to induce GLO1, connecting the TXNIP–GLO1 regulatory circuit.

    Evidence Patient-derived myoblasts and fibroblasts, D-lactate quantification, NRF2 pathway and GLO1 expression analysis

    PMID:40721014

    Open questions at the time
    • Direct NRF2 binding to GLO1 promoter not shown
    • Whether the circuit operates in non-TXNIP-deficient contexts unknown
    • Single patient-derived cell system
  19. 2025 Medium

    GLO1 was shown to promote breast cancer lymph node metastasis by stabilizing GSS against proteasomal degradation, thereby maintaining GSH levels and redox balance and supporting lymphatic angiogenesis.

    Evidence Single-cell RNA-seq, multi-omics, GSS proteasomal degradation assay, GSH/ROS measurement, in vivo metastasis models

    PMID:40492378

    Open questions at the time
    • Direct physical interaction between GLO1 and GSS not demonstrated
    • E3 ligase targeting GSS not identified
    • Whether MG itself or a GLO1 protein interaction stabilizes GSS unclear
  20. 2026 High

    GLO1 enrichment in glioma stem cells and its requirement for GSC viability via Sox2-dependent transcriptional programs established GLO1 as a targetable dependency in glioblastoma stemness maintenance.

    Evidence Single-cell transcriptomics, genetic knockdown/overexpression, pharmacological inhibition, PDX and IUE-GBM mouse models

    PMID:42011505

    Open questions at the time
    • Whether MG directly modifies Sox2 or acts upstream not resolved
    • Resistance mechanisms to GLO1 inhibition in GSCs not explored
    • Biomarker for patient selection not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ligase(s) mediating itaconate-triggered GLO1 degradation, the structural basis by which K157 crotonylation inhibits catalysis, whether GLO1 nuclear translocation serves a distinct non-enzymatic function, and the direct molecular target of MG in neurons that modulates anxiety behavior.
  • E3 ligase for itaconate-driven GLO1 degradation unidentified
  • Structural model of K157-crotonylated GLO1 lacking
  • Nuclear function of GLO1 undefined
  • Neuronal MG receptor/target not molecularly identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016853 isomerase activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 1
Partners
GSSHDAC1HDAC3MMSETSIRT2YBX1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 GLO1 encodes glyoxalase 1, a glutathione-dependent enzyme that detoxifies methylglyoxal (MG), a cytotoxic byproduct of glycolysis. siRNA knockdown of GLO1 sensitized cancer cells to methylglyoxal cytotoxicity, and cells with GLO1 amplification were more sensitive to GLO1 inhibition by bromobenzylglutathione cyclopentyl diester (BBGC), establishing GLO1 as a functional detoxification enzyme required for cell survival under glycolytic stress. RNAi knockdown, pharmacological inhibition, cell accumulation and apoptosis assays Genes, chromosomes & cancer High 20544845
2010 GLO1 knockdown in human metastatic melanoma cells increased methylglyoxal-mediated protein adduction; the major methylglyoxal-adducted protein was identified as heat shock protein 27 (Hsp27/HSPB1) by 2D proteomics and mass spectrometry, identifying Hsp27 as a key cellular substrate of MG when GLO1 is absent. siRNA knockdown, immunodetection with anti-argpyrimidine antibody, 2D proteomics, mass spectrometry Melanoma research Medium 20093988
2014 The GLO1 C332 (Ala111) variant reduces glyoxalase enzymatic activity in leukocytes and post-mortem brain tissue without altering GLO1 protein levels, and is associated with increased AGE formation; a strong negative correlation between glyoxalase activity and AGE levels was demonstrated, establishing a functional consequence of this coding variant on the GLO1-AGE axis. Enzymatic activity assays in leukocytes and post-mortem brain tissue, AGE quantification, genotype-stratified analysis Journal of psychiatric research Medium 25201284
2015 Neuronal-specific overexpression of Glo1 (via Synapsin 1-Cre) is sufficient to increase anxiety-like behavior in mice, and direct microinjection of methylglyoxal (MG) into the basolateral amygdala (BLA) reduced anxiety-like behavior, demonstrating that GLO1 regulates anxiety through neuronal MG levels acting in the amygdala. Conditional transgenic overexpression (ROSA26 knock-in x Syn-CRE), stereotaxic microinjection, behavioral assays Behavioural brain research High 26711908
2016 When Glo1 levels were decreased in embryonic mouse cortical neural precursor cells (NPCs), this caused premature neurogenesis and NPC depletion embryonically and long-term alterations in cortical neurons postnatally; increased circulating maternal methylglyoxal caused similar changes, establishing that the Glo1-MG pathway regulates neural stem cell pool maintenance. Glo1 loss-of-function in embryonic NPCs, maternal MG exposure model, cortical precursor analysis Cell reports High 27760310
2016 GLO1 knockdown (shRNA) in MCF-7 cancer cells significantly reduced tumor-associated properties such as migration and proliferation; GLO1 overexpression in HEK293 cells conferred resistance to hypoxia-induced growth inhibition, indicating that GLO1 activity maintains malignant cell properties and supports growth under hypoxic stress. shRNA knockdown, overexpression, cell migration and proliferation assays, hypoxia experiments International journal of molecular sciences Medium 27999356
2014 GLO1 is translocated into the nucleus to a greater extent in progressive (QRsP-11) compared to regressive (QR-32) murine fibrosarcoma cells; this nuclear translocation is reversed by the MEK inhibitor U0126, and GLO1 siRNA inhibits cell proliferation and migration, placing GLO1 nuclear localization downstream of MEK/ERK signaling. 2D proteomics, MS, MEK inhibitor treatment, siRNA knockdown, subcellular fractionation/immunofluorescence Electrophoresis Medium 24532130
2013 GLO1 knockdown via siRNA in L6 myoblasts under hyperglycemic conditions caused accumulation of methylglyoxal and augmented GLUT4 levels at the cell surface at least in part through reduction of GLUT4 internalization, resulting in increased glucose uptake; NAC (antioxidant/MG scavenger) prevented MG-induced GLUT4 translocation, linking GLO1 to regulation of glucose transporter trafficking. siRNA knockdown, GLUT4 surface expression assay (myc-tagged GLUT4), pharmacological rescue PloS one Medium 23717693
2018 GLO1 inhibition in glioblastoma (GBM) cell lines and in an orthotopic xenograft model increased levels of the DNA-AGE CEdG (N2-1-(carboxyethyl)-2'-deoxyguanosine), substantially elevated RAGE expression, and induced apoptosis; shRNA targeting of GLO1 similarly increased CEdG and RAGE expression, demonstrating that GLO1 protects GBM cells from MG-induced DNA glycation and RAGE-mediated apoptosis. Pharmacological GLO1 inhibition, shRNA knockdown, CEdG biomarker quantification, RAGE expression analysis, orthotopic xenograft model International journal of molecular sciences High 29385725
2018 MMSET I (a short isoform of the t(4;14) myeloma oncoprotein) binds upstream of the GLO1 transcription start site (demonstrated by ChIP-qPCR) and increases GLO1 expression; ectopic overexpression of GLO1 significantly rescued KMS11 myeloma cells from MMSET I knockdown-induced apoptosis and glycolysis inhibition, placing GLO1 as a functional downstream effector of MMSET I. ChIP-qPCR, gene expression array, knockdown and overexpression rescue experiments, apoptosis assays Leukemia High 30470837
2015 Monacolin K reduces GLO1 expression in U937 AML cells through inhibition of the Ras/Raf/ERK/NF-κB and Ras/PI3K/Akt/NF-κB pathways; use of specific pathway inhibitors (U0126, LY294002, JSH-23) confirmed that NF-κB downstream of Ras/ERK and Ras/Akt regulates GLO1 expression and that GLO1 downregulation mediates monacolin K-induced apoptosis. Pharmacological inhibitors, pathway activity assays, apoptosis analysis Journal of agricultural and food chemistry Medium 25569448
2019 Reduction of GLO1 in basilar artery smooth muscle cells (BASMCs) promoted, while overexpression prevented, angiotensin II-induced cell proliferation and cell cycle transition; these effects were mediated through PI3K/AKT/CDK2 cascade activation; in vivo, AAV-mediated GLO1 overexpression improved cerebrovascular remodeling in hypertensive mice, placing GLO1 as a negative regulator of the PI3K/AKT/CDK2 proliferative pathway in vascular smooth muscle. Knockdown and overexpression in BASMCs, signaling pathway analysis, AAV gene delivery in mouse model, histological analysis Biochemical and biophysical research communications High 31420161
2020 CRISPR/Cas9-based GLO1 deletion from A375 melanoma cells upregulated TXNIP (thioredoxin-interacting protein) as the most pronounced expression change; GLO1 deletion also altered glucose metabolism (downregulation of GLUT1, GFAT1, GFAT2, LDHA; depletion of glucose-6-phosphate and UDP-N-acetylglucosamine) and modulated immune checkpoint gene expression (PDL1). Treatment with MG or a GLO1 inhibitor mimicked the GLO1 KO effect on TXNIP, indicating GLO1 controls TXNIP expression via MG regulation. CRISPR/Cas9 knockout, NanoString gene expression profiling, RT-qPCR, immunoblot, metabolite analysis, pharmacological mimicry Redox biology High 33360689
2025 Itaconate promotes proteasomal degradation of GLO1 via Cys139 alkylation in macrophages, leading to MGO and AGE accumulation and exacerbating inflammatory responses; elevated itaconate in sepsis patients correlated with reduced GLO1 in PBMCs, and myeloid-specific AGER knockout mice showed reduced inflammation and improved survival in sepsis, linking itaconate-driven GLO1 degradation to the inflammatory AGE/RAGE axis. Proteasomal degradation assay, site-directed mutagenesis (Cys139), patient PBMC analysis, conditional knockout mouse model of sepsis Biochemical and biophysical research communications High 39787788
2025 Crotonylation of GLO1 at lysine 157 (K157) was found at higher levels in saphenous vein (SV) compared to internal thoracic artery (ITA) grafts; site-specific GLO1 crotonylation decreased enzymatic activity and was associated with elevated methylglyoxal accumulation and increased oxidative stress. Overexpression of HDAC1/HDAC3 reversed GLO1 crotonylation and restored activity. CBP inhibition reversed SV oxidative stress. PTM proteomics, site-mutation experiments in HEK293 cells, HDAC overexpression, ex vivo cultured ITA/SV tissue, pharmacological inhibition Redox biology High 40138913
2024 SIRT2 knockdown attenuated GLO1 protein by ~28% and activity by ~42% in human myotubes; NAMPT knockdown also reduced GLO1 protein, activity, and transcripts; neither manipulation altered GLO1 acetylation status, suggesting NAD+-dependent regulation of GLO1 expression and activity independent of direct acetylation. siRNA knockdown of SIRT2 and NAMPT, GLO1 activity assays, acetylation immunoprecipitation, NR/NMN supplementation Redox biology Medium 39142179
2022 lncRNA RP11-162G10.5 recruits the transcription factor YBX1 to the GLO1 promoter, activating GLO1 transcription in breast cancer; this was demonstrated by ChIP and rescue experiments showing that YBX1 or GLO1 knockdown reversed RP11-162G10.5-driven tumor promotion. ChIP, luciferase reporter assay, knockdown and rescue experiments, in vivo xenograft Cellular oncology (Dordrecht, Netherlands) Medium 36576700
2024 CircMAN1A2_009 interacts with YBX1, facilitating phosphorylation of YBX1 at serine 102 (p-YBX1-S102) and promoting YBX1 nuclear localization via sequence 245–251, which in turn increases GLO1 promoter activity and GLO1 expression in cervical adenocarcinoma cells. Co-immunoprecipitation, luciferase reporter assay, knockdown/overexpression, nuclear localization imaging Cancer science Medium 39038813
2025 In TXNIP-deficient patient-derived primary myoblasts and fibroblasts, NRF2 activation was associated with upregulation of GLO1; increased GLO1 led to elevated D-lactate production (downstream product of MG detoxification), suggesting that TXNIP deficiency causes increased glycolytic MGO flux that activates NRF2, which in turn induces GLO1 expression. Patient-derived primary cells, D-lactate quantification, NRF2 pathway analysis, GLO1 expression/activity measurement Free radical biology & medicine Medium 40721014
2025 In a yeast model (ortholog study), absence of Glo1 greatly elevated MG-induced genome-wide mutagenesis in single-stranded DNA; MG mutagenesis occurred via a guanine-centered strand slippage and mispairing mechanism requiring the translesion polymerase Rev1. This establishes that GLO1/Glo1 protects genome integrity from MG-induced mutagenesis via a defined Rev1-dependent mechanism. Yeast Glo1 deletion, whole-genome mutation spectrum analysis, Rev1 deletion epistasis, aminoguanidine quencher rescue bioRxivpreprint Medium bio_10.1101_2025.03.18.643935
2026 Glo1 is enriched in glioma stem cell (GSC) populations defined by stemness markers; genetic knockdown or pharmacological inhibition of Glo1 reduced GSC viability and tumor growth and prolonged survival in PDX and IUE-GBM mouse models. Mechanistically, Glo1 modulation disrupted transcriptional programs associated with GSC maintenance by modulating Sox2 activity. Single-cell transcriptomics, genetic overexpression/knockdown, pharmacological inhibition, PDX and IUE preclinical GBM models, Sox2 activity analysis Neuro-oncology High 42011505
2025 GLO1 promotes lymph node metastasis in breast cancer partly by inhibiting proteasomal degradation of glutathione synthetase (GSS), thereby maintaining intracellular glutathione (GSH) and reactive oxygen species (ROS) balance, and by promoting lymphatic angiogenesis. Single-cell RNA sequencing, multi-omics, experimental validation (proteasome inhibition, GSH/ROS measurement), in vitro and in vivo metastasis assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40492378
2024 Butyrate (NaB) inhibits the JAK2/STAT3/Nrf2/Glo1 pathway in castration-resistant prostate cancer cells (DU145); co-treatment with the STAT3 activator Colivelin reversed NaB effects on GLO1 expression, MG-H1 production, and cell viability; overexpression of STAT3 or GLO1 reduced NaB-induced cell death, placing GLO1 downstream of JAK2/STAT3/Nrf2 as a survival effector. Pharmacological inhibition/activation, overexpression rescue, pathway protein analysis, MGO adduct quantification Oncology reports Medium 38577936

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 C. elegans RPM-1 regulates axon termination and synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1. Neuron 113 17698012
2010 GLO1-A novel amplified gene in human cancer. Genes, chromosomes & cancer 95 20544845
2009 A common and unstable copy number variant is associated with differences in Glo1 expression and anxiety-like behavior. PloS one 91 19266052
2012 Role of Glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior: recent advances and mechanistic insights. Frontiers in genetics 90 23181072
2010 GLO1 overexpression in human malignant melanoma. Melanoma research 80 20093988
2020 Morroniside attenuates high glucose-induced BMSC dysfunction by regulating the Glo1/AGE/RAGE axis. Cell proliferation 76 32643284
2009 CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study. BMC cancer 71 19379515
2019 Glycine Suppresses AGE/RAGE Signaling Pathway and Subsequent Oxidative Stress by Restoring Glo1 Function in the Aorta of Diabetic Rats and in HUVECs. Oxidative medicine and cellular longevity 62 30944692
2021 Inosine mitigated diabetic peripheral neuropathy via modulating GLO1/AGEs/RAGE/NF-κB/Nrf2 and TGF-β/PKC/TRPV1 signaling pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 55 34775239
1983 Mapping SB in relation to HLA and GLO1 using cells from first-cousin marriage offspring. Immunogenetics 54 6417008
2003 The globby1-1 (glo1-1) mutation disrupts nuclear and cell division in the developing maize seed causing alterations in endosperm cell fate and tissue differentiation. Development (Cambridge, England) 53 12952903
2012 Glyoxalase I (GLO1) is up-regulated in pancreatic cancerous tissues compared with related non-cancerous tissues. Anticancer research 48 22843895
2007 Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1. BMC medical genetics 46 17346350
2016 A Glo1-Methylglyoxal Pathway that Is Perturbed in Maternal Diabetes Regulates Embryonic and Adult Neural Stem Cell Pools in Murine Offspring. Cell reports 43 27760310
2020 Genomic GLO1 deletion modulates TXNIP expression, glucose metabolism, and redox homeostasis while accelerating human A375 malignant melanoma tumor growth. Redox biology 42 33360689
2014 Glo1 genetic amplification as a potential therapeutic target in hepatocellular carcinoma. International journal of clinical and experimental pathology 39 24966916
2021 Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2/Glo1 Pathway. Antioxidants (Basel, Switzerland) 35 34062923
2020 LncRNA OIP5-AS1 Promotes Breast Cancer Progression by Regulating miR-216a-5p/GLO1. The Journal of surgical research 33 32916503
2018 Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis. PLoS genetics 32 30419011
2018 Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models. International journal of molecular sciences 30 29385725
2012 Glycolate oxidase isozymes are coordinately controlled by GLO1 and GLO4 in rice. PloS one 30 22761858
2020 Discovery of GLO1 New Related Genes and Pathways by RNA-Seq on A2E-Stressed Retinal Epithelial Cells Could Improve Knowledge on Retinitis Pigmentosa. Antioxidants (Basel, Switzerland) 29 32413970
2018 GLO1 gene polymorphisms and their association with retinitis pigmentosa: a case-control study in a Sicilian population. Molecular biology reports 29 30099685
2016 Modulation of GLO1 Expression Affects Malignant Properties of Cells. International journal of molecular sciences 26 27999356
2006 Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r). American journal of physiology. Regulatory, integrative and comparative physiology 26 16946080
2018 miR-137 inhibits melanoma cell proliferation through downregulation of GLO1. Science China. Life sciences 25 29307109
2025 Paracrine Orchestration of Tumor Microenvironment Remodeling Induced by GLO1 Potentiates Lymph Node Metastasis in Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 40492378
2015 Neuronal overexpression of Glo1 or amygdalar microinjection of methylglyoxal is sufficient to regulate anxiety-like behavior in mice. Behavioural brain research 20 26711908
2014 Proteomic analysis indicates that overexpression and nuclear translocation of lactoylglutathione lyase (GLO1) is associated with tumor progression in murine fibrosarcoma. Electrophoresis 20 24532130
2014 The GLO1 C332 (Ala111) allele confers autism vulnerability: family-based genetic association and functional correlates. Journal of psychiatric research 19 25201284
2013 Impact of GLO1 knock down on GLUT4 trafficking and glucose uptake in L6 myoblasts. PloS one 18 23717693
2018 MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells. Leukemia 17 30470837
2022 H3K27 acetylation activated long noncoding RNA RP11-162G10.5 promotes breast cancer progression via the YBX1/GLO1 axis. Cellular oncology (Dordrecht, Netherlands) 15 36576700
2015 Blockade of the Ras/Raf/ERK and Ras/PI3K/Akt Pathways by Monacolin K Reduces the Expression of GLO1 and Induces Apoptosis in U937 Cells. Journal of agricultural and food chemistry 15 25569448
2014 Weak association of glyoxalase 1 (GLO1) variants with autism spectrum disorder. European child & adolescent psychiatry 14 24671236
2008 Lack of evidence to support the glyoxalase 1 gene (GLO1) as a risk gene of autism in Han Chinese patients from Taiwan. Progress in neuro-psychopharmacology & biological psychiatry 14 18721844
2021 FAM201A knockdown inhibits proliferation and invasion of lung adenocarcinoma cells by regulating miR-7515/GLO1 axis. Journal of cellular physiology 13 33687075
2018 Glyoxalase 1 (GLO1) Inhibition or Genetic Overexpression Does Not Alter Ethanol's Locomotor Effects: Implications for GLO1 as a Therapeutic Target in Alcohol Use Disorders. Alcoholism, clinical and experimental research 10 29532486
2014 Glyoxalase I (Glo1) and its metabolites in vascular disease. Biochemical Society transactions 10 24646273
2024 Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells. Oncology reports 9 38577936
2020 Expression of Brassica napus GLO1 is sufficient to breakdown artificial self-incompatibility in Arabidopsis thaliana. Plant reproduction 8 32862319
2020 Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats. Antioxidants (Basel, Switzerland) 7 33255888
2019 Reduction of glyoxalase 1 (GLO1) aggravates cerebrovascular remodeling via promoting the proliferation of basilar smooth muscle cells in hypertension. Biochemical and biophysical research communications 7 31420161
1988 Analysis for linkage between F13A and three chromosome 6 marker loci: evidence for 6pter:F13A:HLA:GLO1:cen gene order. Human genetics 7 2900213
2024 GLO1 regulates hepatocellular carcinoma proliferation and migration through the cell cycle pathway. BMC cancer 6 39434012
2023 MiR-205-3p suppresses bladder cancer progression via GLO1 mediated P38/ERK activation. BMC cancer 6 37814205
2020 Syzygium aromaticum Reduces Diabetes-induced Glucotoxicity via the NRF2/Glo1 Pathway. Planta medica 6 32645736
2016 The GLO1 Gene Is Required for Full Activity of O-Acetyl Homoserine Sulfhydrylase Encoded by MET17. ACS chemical biology 6 27935278
2025 Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE/RAGE glycosylation. Frontiers in pharmacology 5 40635755
2023 Molecular Link between Glo-1 Expression and Markers of Hyperglycemia and Oxidative Stress in Vascular Complications of Type 2 Diabetes Mellitus. Antioxidants (Basel, Switzerland) 5 37759966
2025 Itaconate drives pro-inflammatory responses through proteasomal degradation of GLO1. Biochemical and biophysical research communications 4 39787788
2025 Protein post-translational modification crotonylation of TXN and GLO1 in artery and vein grafts for coronary artery surgery. Redox biology 4 40138913
2023 Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study. Frontiers in endocrinology 4 38027126
2019 High expression of GLO1 indicates unfavorable clinical outcomes in glioma patients. Journal of neurosurgical sciences 4 31738028
2025 Glo1 reduction in mice results in age- and sex-dependent metabolic dysfunction. bioRxiv : the preprint server for biology 3 39896461
2024 CircMAN1A2_009 facilitates YBX1 nuclear localization to induce GLO1 activation for cervical adenocarcinoma cell growth. Cancer science 3 39038813
2010 Mismatched multiplex PCR amplification and subsequent RFLP analysis to simultaneously identify polymorphisms of erythrocytic ESD, GLO1, and GPT genes. Journal of forensic sciences 3 21198613
1988 Population polymorphism of the GLO1 enzyme. Identification of two new variants. Gene geography : a computerized bulletin on human gene frequencies 3 3154776
2025 Patient-derived TXNIP-deficient primary cells exhibit NRF2 activation linked to upregulation of glyoxalase 1 (GLO1). Free radical biology & medicine 2 40721014
2024 Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy. Pakistan journal of medical sciences 2 38545031
2024 Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle. Redox biology 2 39142179
2025 Gender-Dependent Cognitive and Metabolic Benefits Due to Glyoxalase 1 (Glo1) Overexpression in Age-Accelerated SAMP8 Mice. Antioxidants (Basel, Switzerland) 1 40867843
2022 GLO1 Contributes to the Drug Resistance of Escherichia coli Through Inducing PER Type of Extended-Spectrum β-Lactamases. Infection and drug resistance 1 35414749
1991 ESD, GLO1, PGD, PGM1 and PGM2 gene frequencies in the Salerno Province (Italy). Gene geography : a computerized bulletin on human gene frequencies 1 1840292
1990 Genetic polymorphisms of HLA class III and GLO1 in Chinese Yao nationality. Gene geography : a computerized bulletin on human gene frequencies 1 2278900
2026 Systems genomics reveals age- and sex-dependent metabolic dysregulation from Glo1 reduction in mice. Physiological genomics 0 41543389
2026 Glo1 promotes glioma progression by modulating Sox2 transcriptional networks in glioma stem-like cells. Neuro-oncology 0 42011505
2025 Pharmacological and genetic manipulation of glyoxalase-1 (GLO1) does not alter locomotor responses or conditioned place preference induced by cocaine or oxycodone. Pharmacology, biochemistry, and behavior 0 40412584
2024 Sanger Sequencing Reveals Novel Variants in GLO-1, ACE, and CBR1 Genes in Patients of Early and Severe Diabetic Nephropathy. Medicina (Kaunas, Lithuania) 0 39336582
2001 [The Russian gene pool. Genogeography of erythrocyte genetic markers (ACP1, PGM1, ESD, GLO1, 6-PGD)]. Genetika 0 11642115
1991 [Genetic structure of the Mongols as derived from the ABO, MN, Rh, EsD, GLO1, PGM1, AcP, 6-PGD, Hp, Gc, Tf, C'3 and ChE2 loci]. Genetika 0 1908400
1989 [Distributions and gene frequencies of PGM1 subtype, EsD, GLO1, AK, ADAand 6-PGD in 20 races of China]. Yi chuan xue bao = Acta genetica Sinica 0 2534281
1984 [Population genetics of taiga hunters and reindeer breeders in central Siberia. The biochemical markers of genes Hp, Tf, Gc, A1b, GLO1, PGM1, AcP and EsD]. Genetika 0 6542041