Ask about this productRelated genes to: EIF2AK3 antibody
- Gene:
- EIF2AK3 NIH gene
- Name:
- eukaryotic translation initiation factor 2 alpha kinase 3
- Previous symbol:
- -
- Synonyms:
- PEK, PERK
- Chromosome:
- 2p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-06-14
- Date modifiied:
- 2019-04-23
Related products to: EIF2AK3 antibody
Related articles to: EIF2AK3 antibody
- Glutaric acidemia type 1 (GA I) is caused by deficient activity of glutaryl-CoA dehydrogenase, leading to predominant accumulation of glutaric acid (GA) in the brain. GA I patients present progressive neurological deterioration whose pathophysiology is only partially elucidated. We investigated whether intracerebral GA administration, alone or combined with quinolinic acid (QA), a pro-inflammatory intermediate of the kynurenine pathway, could alter the expression of genes associated with inflammatory signaling, endoplasmic reticulum (ER) stress, and neurotrophic support in cerebral cortex of wild-type (WT) and Gcdh mice. We also tested the effects of L-carnitine (Carn) on these parameters. GA alone increased mRNA levels of the genes encoding NF-κB (NFKB1), COX-2 (PTGS2), iNOS (NOS2), and TLR2 (TLR2) in both genotypes, while reducing those of IL-10 (IL10) and VEGF-A (VEGFA) only in Gcdh mice. Combined QA + GA treatment produced a larger response, including increased TNF-α (TNF), IL-1β (IL1B), IL-6 (IL6), NLRP3 (NLRP3), CHOP (DDIT3) and PERK (EIF2AK3) mRNA levels in the Gcdh mice, besides reducing IκBα (NFKBIA), IL-10 (IL10) and BDNF (BDNF) expression in both genotypes, and VEGF-A (VEGFA) in the Gcdh mice. We also found that lysine (Lys) and QA treatment elevated TNF-α, IL-1β, and IL-6 protein levels in Gcdh mice. Carn prevented or attenuated most transcriptional alterations induced by QA + GA and reduced cytokine protein elevations elicited by Lys + QA administration. These findings indicate that Carn modulates acute molecular responses related to inflammation, ER stress, and neurotrophic factors in the cerebral cortex of the GAI mouse model. - Source: PubMed
Publication date: 2026/09/05
Castro Ediandra TissotZanatta ÂngelaCarvalho Andrey Vinicios Soaresde Moraes Amanda UggeriNetto Carlos AlexandreLeipnitz GuilhianAmaral Alexandre UmpierrezVargas Carmen ReglaRibeiro Rafael TeixeiraWajner Moacir - Deep intronic variants can disrupt splicing and cause monogenic disease but are missed by routine genetic testing. This study assessed the contribution of deep intronic variants to Wolcott-Rallison syndrome (WRS), a recessive disorder characterized by early-onset diabetes and progressive multisystem disease caused by loss-of-function EIF2AK3 variants. - Source: PubMed
Publication date: 2026/09/03
Al Assi AlaaBonfield GeorgiaRuss-Silsby JamesAhmed SuhelLaver Thomas WKaraer KadriÖzhan BayramAltincik AycaPatel Kashyap AHoughton Jayne A LFlanagan Sarah EJohnson Matthew BDe Franco Elisa - ER stress (ERS) influences tumor behavior through the unfolded protein response (UPR), yet its role in glioma is not fully defined. This study investigated the function of the ERS-related regulator QRICH1 in glioma progression. - Source: PubMed
Wang YunjiangXu MinChen ZhenglouHuo XuqiXue YaJi XiangShen YangWang Hongsheng - Clear cell renal cell carcinoma (ccRCC) exhibits a paradoxical fructose metabolism signature characterized by upregulation of the fructose transporter GLUT5 alongside downregulation of the catabolic enzymes (ketohexokinase, aldolase B, and triokinase), a pattern associated with poor prognosis. Functionally, unlike the pro-survival effect of fructose under glucose deprivation, in the presence of glucose, fructose co-treatment suppresses ccRCC cell proliferation, and induces profound mitochondrial dysfunction, including impaired oxidative phosphorylation, loss of membrane potential, excessive mitochondrial superoxide production, reduced mtDNA copy number, and downregulation of mitochondria-encoded electron transport chain subunits (notably ND2 and ND4 of complex I). Mechanistically, co-treatment with glucose and fructose creates a metabolic trap resulting in fructose-1-phosphate accumulation and ATP depletion. This energy crisis drives profound depletion of purine and pyrimidine nucleotide pools, which selectively triggers the PERK-eIF2S1-ATF4-CHOP axis of the integrated stress response, thereby mediating mitochondrial impairment and ultimately sensitizing ccRCC cells to intrinsic apoptosis via BID cleavage and caspase-3 activation under nutrient stress. Pharmacological treatment with the chemical chaperone 4-phenylbutyric acid (4-PBA) or nucleoside supplementation reverses mitochondrial dysfunction and fructose-induced cytotoxicity. The tumor-suppressive effect of fructose is validated in patient-derived organoids and xenograft mouse models, where fructose administration significantly attenuates tumor growth via ER stress. These findings reveal fructose-driven nucleotide depletion and PERK-dependent ER stress leading to mitochondrial dysfunction, which underlies the tumor-suppressive toxicity of fructose and exposes a targetable metabolic vulnerability in ccRCC. - Source: PubMed
Publication date: 2026/08/07
Li NaDing YanhongYu BowenWang YongqiangGao TongbinYin HuiyongLi ZhenhuaLiu ShuzhenYu GuohuaWang Ningning - Cardiovascular diseases remain the leading cause of mortality worldwide, and endoplasmic reticulum (ER) stress has emerged as an important molecular mechanism underlying myocardial injury and heart failure. This study investigated the expression of the ER stress-related genes GRP78, PERK, and CHOP in peripheral whole blood obtained from patients with acute cardiovascular diseases. A total of 300 participants were enrolled, including 200 patients with ST-segment elevation myocardial infarction (STEMI, = 55), non-ST-segment elevation myocardial infarction (NSTEMI, = 88), decompensated heart failure (DHF, = 40), or unstable angina pectoris (USAP, = 17), and 100 healthy controls. Relative mRNA expression levels were quantified using quantitative real-time PCR. Intergroup comparisons were performed using the Kruskal-Wallis test followed by Dunn's post hoc test with Bonferroni adjustment. Significant differences in GRP78, PERK, and CHOP expression were observed among the study groups (all < 0.001). GRP78 and PERK expression levels were highest in the STEMI and DHF groups, whereas CHOP expression was highest in the STEMI group. Significant positive correlations were identified between troponin and CHOP ( = 0.48), GRP78 ( = 0.42), and PERK ( = 0.39) (all < 0.001), while weaker but significant associations were observed between inflammatory markers (CRP and NLR) and ER stress-related gene expression. Exploratory receiver operating characteristic (ROC) analysis showed that CHOP demonstrated the highest discriminatory performance for distinguishing patients with acute cardiovascular disease from healthy controls. These findings indicate that peripheral whole-blood ER stress-related gene expression is associated with acute cardiovascular disease and correlates with established biomarkers of myocardial injury and inflammation. Further prospective studies are required to determine the clinical significance of these findings. - Source: PubMed
Publication date: 2026/08/14
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