| 2005 |
The V175M substitution in human PEMT (exon 8 SNP) is a loss-of-function mutation, as demonstrated by transient transfection of McArdle-RH7777 cells with wild-type versus V175M mutant PEMT constructs, showing diminished enzymatic activity. |
Transient transfection of hepatoma cells with wild-type vs. V175M mutant PEMT constructs; enzymatic activity assay |
FASEB journal |
Medium |
16051693
|
| 2003 |
PEMT (encoded by Pemt-2) is the sole de novo choline-synthesizing enzyme in the liver; Pemt-/- mice fed any level of dietary choline develop hepatic steatosis, elevated apoptosis (TUNEL-positive cells), and reduced phosphatidylcholine concentrations, demonstrating that PEMT activity is required for normal hepatic phospholipid homeostasis and is not fully compensable by dietary choline. |
Pemt-/- knockout mouse model with dietary choline manipulation; liver histology, TUNEL assay, choline metabolite quantification |
The Biochemical journal |
High |
12466019
|
| 2010 |
Estrogen regulates PEMT in an isoform-specific fashion; chromatin immunoprecipitation identified estrogen receptor binding regions in the PEMT locus, and the risk SNP rs12325817 (located within 1 kb of the critical estrogen response element) abrogates binding of both the estrogen receptor and the pioneer factor FOXA1, preventing hormone-inducible PEMT expression. |
Transcript-specific gene expression analysis, locus-wide SNP analysis, chromatin immunoprecipitation with locus-wide microarray (ChIP-chip) |
The Journal of biological chemistry |
High |
21059658
|
| 2002 |
Liver damage caused by PEMT deficiency combined with choline-deficient diet is rapidly reversible upon choline supplementation, demonstrating that PEMT's essential role is to supply choline/phosphatidylcholine for hepatocyte survival. |
Pemt-/- mouse dietary rescue experiment; plasma aminotransferase assays, hepatic PC and triacylglycerol measurement |
The Journal of nutrition |
Medium |
11773510
|
| 2019 |
Protection against diet-induced obesity and insulin resistance in Pemt-/- mice is specifically dependent on hepatic PEMT activity (not extrahepatically expressed PEMT); restoration of hepatic PEMT via adeno-associated virus in Pemt-/- mice reversed protection against obesity and insulin resistance, while AAV-mediated restoration also worsened the PC:PE ratio and NAFLD, demonstrating that hepatic PEMT is the critical site of action. |
Adeno-associated virus-mediated hepatic PEMT restoration in Pemt-/- mice; antisense oligonucleotide knockdown of hepatic PEMT in wild-type and ob/ob mice; measurement of weight gain, insulin sensitivity, liver function, and hepatic PC:PE ratio |
FASEB journal |
High |
31284753
|
| 2000 |
PEMT2 protein and mRNA are lost in pre-neoplastic nodules and hepatocellular carcinoma induced by aflatoxin B1 without gene deletion or mutation, indicating transcriptional downregulation. Re-expression of PEMT2 in McArdle hepatoma cells inhibited anchorage-independent colony formation and reduced tumorigenicity in athymic mice, demonstrating a tumor-suppressive function. |
Western blot, RT-PCR, Southern blot in rat liver carcinogenesis model; transfection of PEMT2 into McArdle hepatoma cells; soft-agar colony assay; xenograft tumorigenicity assay in athymic mice |
International journal of cancer |
Medium |
10760824
|
| 2002 |
Overexpression of PEMT2 in rat hepatoma CBRH-7919 cells downregulates multiple components of the PI3K/Akt signaling pathway (c-Met, PDGF receptor, PI3K, Akt, Bcl-2) and induces apoptosis, linking PEMT2-mediated phospholipid changes to suppression of a major cell-survival pathway. |
Stable transfection of PEMT2 cDNA into hepatoma cells; Western blotting for PI3K/Akt pathway proteins; flow cytometry and DNA ladder apoptosis assays; pharmacological inhibitors (wortmannin, PD98059) |
Biochimica et biophysica acta |
Medium |
11960751
|
| 2009 |
PEMT2-overexpressing hepatoma cells produce phosphatidylcholine enriched in oleic acid that localizes mainly to mitochondria; PEMT2 overexpression increases mitochondrial membrane fluidity, triggers cytochrome C release, and activates caspase-9 and caspase-3, establishing a mitochondrial (intrinsic) apoptotic pathway downstream of PEMT2 activity. |
Stable PEMT2 transfection in CBRH-7919 cells; lipid extraction with HPTLC and GC; [3H]-ethanolamine tracing; Western blot for cytochrome C and caspase activation; membrane fluidity measurement |
IUBMB life |
Medium |
19517528
|
| 2004 |
Deletion of Pemt results in increased S-adenosylmethionine levels and elevated DNA and protein methylation in fetal hippocampus, accompanied by increased neural progenitor cell mitosis and decreased GABAergic neuronal differentiation (calretinin expression), placing PEMT in a pathway regulating hippocampal development through methylation substrate availability. |
Pemt-/- knockout mouse; phosphorylated histone H3 immunostaining (mitosis marker); calretinin immunostaining; SAM quantification; DNA and protein methylation assays in embryonic day 17 hippocampus |
Brain research. Developmental brain research |
Medium |
15063092
|
| 2009 |
Pemt-/- fetal brains have 25-50% less phospholipid-DHA compared to wild-type; dietary DHA supplementation to pregnant Pemt-/- dams restores fetal brain phospholipid-DHA to wild-type levels and abrogates abnormal neural progenitor proliferation and apoptosis, demonstrating that PEMT's role in fetal hippocampal development is mediated through DHA incorporation into membrane phospholipids. |
Pemt-/- knockout mouse with dietary DHA supplementation; phospholipid-DHA quantification; BrdU/Ki67 proliferation assay; TUNEL apoptosis assay; calretinin immunostaining in E17 hippocampus |
The Journal of biological chemistry |
Medium |
19889625
|
| 2014 |
PEMT promoter methylation at the -132 site in BRCA1-mutated breast cancer leads to loss of active histone mark H3K9ac and gain of repressive mark H3K9me3, synergistically inhibiting PEMT transcription; this identifies DNA methylation and histone modification as cooperating epigenetic regulators of PEMT expression. |
Bisulfite sequencing; chromatin immunoprecipitation for H3K9ac and H3K9me3; transcript-specific expression analysis in breast cancer specimens |
Oncotarget |
Medium |
24675476
|
| 2014 |
PEMT deficiency in mice ameliorates ER stress in diabetic nephropathy; in renal proximal tubular cells, shRNA-mediated Pemt knockdown reduced GRP78 expression (ER stress marker), increased Akt phosphorylation, and decreased cleavage of caspase-3 and caspase-7, demonstrating that PEMT activity promotes ER stress-induced apoptosis in diabetic kidney disease. |
Streptozotocin-induced diabetic Pemt-/- mice; shRNA lentivirus knockdown in mProx24 cells; ER stress induction with tunicamycin/thapsigargin; Western blot for GRP78, p-Akt, caspase-3/-7; histology for glomerular hypertrophy, fibrosis, macrophage infiltration |
PloS one |
Medium |
24667182
|
| 2005 |
Mdr2+/- mice (which secrete 40% less phosphatidylcholine) show significantly lower PEMT activity and higher SAM:SAH ratios compared to Mdr2+/+ mice on a methionine- and choline-deficient diet, and are protected from diet-induced steatohepatitis, placing PEMT activity downstream of hepatic phosphatidylcholine demand and upstream of NASH pathogenesis. |
Mdr2+/- mice fed methionine-choline-deficient diet; PEMT activity assay; SAM/SAH quantification; serum ALT; liver histology |
Journal of hepatology |
Medium |
16376450
|
| 2017 |
Hepatic PEMT protein levels and activity are increased at gestational day 15 and 20 in pregnant rats, coinciding with increased plasma 16:0/DHA-phosphatidylcholine, identifying PEMT as the mechanism for the pregnancy-associated rise in circulating DHA-enriched PC. |
Rat pregnancy time-course study; PEMT activity assay; Western blot for PEMT protein; fatty acid profiling by GC; lipidomics for DHA-PC species |
Journal of lipid research |
Medium |
29167412
|
| 2019 |
Global Pemt-/- mice completely lack UCP1 protein in brown adipose tissue (BAT) without changes in UCP1 mRNA, due to an untranslated UCP1 splice variant induced perinatally; this effect is non-cell-autonomous — BAT-specific, adipose-specific, liver-specific, and muscle-specific PEMT knockouts all maintain normal UCP1 protein levels — demonstrating that PEMT in non-adipocyte cells communicates to BAT to regulate UCP1 splicing during embryonic development. |
Multiple conditional PEMT knockout mouse models (BAT-specific, adipose-specific, liver-specific, muscle-specific); Western blot for UCP1 protein; RT-PCR for UCP1 mRNA and splice variants; cold tolerance testing |
Molecular metabolism |
High |
31918922
|
| 2015 |
High-fat diet-fed Pemt-/- mice develop hypothermia on cold exposure due to plasma hypoglycemia caused by compromised hepatic gluconeogenesis; choline supplementation normalizes plasma glucose, gluconeogenic protein expression, and cold tolerance, establishing a mechanistic link between PEMT activity, hepatic phospholipid balance, and gluconeogenesis. |
HF diet-fed Pemt-/- mice; acute cold exposure (4°C); plasma glucose and catecholamine measurement; lipolysis assay; Western blot for gluconeogenic proteins; choline supplementation rescue |
Journal of lipid research |
Medium |
26113536
|
| 2018 |
Hepatic PEMT expression (restored via AAV in Pemt-/-/Ldlr-/- mice) increases plasma cholesterol and trimethylamine-N-oxide (TMAO) and reverses protection against atherosclerosis, demonstrating that hepatic PEMT-derived choline is the source of substrate for gut microbiota-dependent TMAO production and that PEMT is a mechanistic link between de novo choline synthesis and atherosclerosis risk. |
AAV-mediated hepatic PEMT restoration in Pemt-/-/Ldlr-/- mice; plasma lipid and TMAO quantification; aortic lesion quantification; choline supplementation comparison |
The Journal of nutrition |
Medium |
30281112
|
| 2006 |
PEMT2 overexpression in rat hepatoma cells inhibits phosphorylation and membrane translocation of PLCγ1 and reduces autophosphorylation of c-Met, indicating that PEMT2-induced changes in membrane phospholipid composition downregulate the c-Met/PLCγ1 signaling pathway. |
PEMT2 stable transfection in CBRH-7919 cells; Western blot for PLCγ1 phosphorylation and subcellular fractionation; Western blot for phospho-c-Met |
Zhonghua gan zang bing za zhi |
Low |
16867273
|
| 2005 |
PEMT2 overexpression in CBRH-7919 hepatoma cells inhibits cPKCα expression while increasing cPKCβ2 expression and its translocation from cytosol to plasma membrane, and decreases diacylglycerol (DAG) content, linking PEMT2-mediated phospholipid metabolism to differential regulation of PKC isoforms. |
PEMT2 stable transfection; immunocytochemistry and Western blot for PKC isoforms; HPTLC for DAG quantification |
Zhonghua gan zang bing za zhi |
Low |
16174458
|
| 2023 |
HCV infection induces PEMT expression and uses the PEMT-mediated non-canonical phosphatidylcholine synthesis pathway to increase phosphatidylcholine in the endoplasmic reticulum; siRNA knockdown of PEMT inhibits HCV replication and reverses virus-induced lipogenic gene expression changes (SREBP1c, DGAT1 upregulation; MTP downregulation), establishing PEMT as necessary for HCV-induced steatosis and virus replication. |
HCV cell culture model; quantitative lipidomics (HPTLC/MS); siRNA knockdown of PEMT; Western blot for PEMT and lipogenic genes; qRT-PCR; analysis of liver biopsies from HCV genotype 1 vs. 3 patients |
International journal of molecular sciences |
Medium |
37240132
|
| 2025 |
PEMT physically interacts with SHMT1 in astrocytes; disruption of this interaction depletes SAM, causing H3K4me1 hypomethylation and reduced expression of Slc1a2 and Glul, ultimately exacerbating neuroexcitotoxicity and dopaminergic neuronal loss in a Parkinson's disease model. |
Astrocyte-specific conditional Shmt1 knockout; 13C-serine isotopic labeling; co-immunoprecipitation of SHMT1 and PEMT; ChIP for H3K4me1; gene expression analysis; PD mouse model behavioral and histological assessment |
Advanced science |
Medium |
41262011
|
| 2025 |
Aging-driven PEMT overexpression (~2.4-fold at protein level in 24-month vs. 6-month mice) promotes hepatic phospholipid imbalance (increased PC/PE ratio ~2.5-fold); PEMT inhibition in D-galactose-induced senescent AML12 hepatocytes reduces lipid droplet accumulation by ~30% and intracellular triglycerides by ~20% under lipid stress, mechanistically linking elevated PEMT activity to age-associated hepatic steatosis. |
Natural aging mouse model (2-24 months); lipidomics; Western blot for PEMT protein; siRNA PEMT inhibition in senescent AML12 hepatocytes; lipid droplet quantification; intracellular TG measurement |
The FEBS journal |
Medium |
41311052
|