Ask about this productRelated genes to: OXCT1 antibody
- Gene:
- OXCT1 NIH gene
- Name:
- 3-oxoacid CoA-transferase 1
- Previous symbol:
- OXCT
- Synonyms:
- SCOT
- Chromosome:
- 5p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-05
- Date modifiied:
- 2018-07-11
Related products to: OXCT1 antibody
Related articles to: OXCT1 antibody
- Colorectal cancer (CRC) is one of the most common malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality. Hypoxia and pyroptosis are closely linked to malignant progression and may shape tumour biology and the immune microenvironment. - Source: PubMed
Publication date: 2026/04/22
Wang HuiChen YuanWang - Diabetes heightens cardiovascular risk. The selective sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) shows cardiovascular benefits in heart failure, type 2 diabetes and chronic kidney disease. While EMPA protects against myocardial ischemia/reperfusion injury (MIRI) in diabetic and non-diabetic hearts, its mechanisms and impact on specific endpoints, including autophagy, angiocrine signaling, and metabolic flexibility, remain incompletely defined. We explored the systemic and myocardial effects of chronic EMPA pretreatment on these endpoints in diabetic and non-diabetic animals subjected to MIRI. In streptozotocin (STZ, 65 mg/kg) diabetic rats, EMPA (15 mg/kg/d, 4 weeks) reduced water intake without affecting hyperphagia or weight loss. EMPA ameliorated glucose and lipid profiles, tended to restore myocardial GLUT4 and counteract alterations in myocardial hydroxymethylglutaryl-CoA synthase (HMGCS2) and 3-oxoacid CoA-transferase 1 (OXCT1) levels. EMPA improved biomarkers of myocardial damage (BNP, NT-proBNP, CK-MB, galectin 3), inflammation (cardiac NLRP3, plasma IL-1β), oxidative stress (plasma SOD and malondialdehyde), angiocrine imbalance (VEGF and apelin), fibrosis, and collagen deposition, while showing a tendency to improve autophagy and apoptosis signaling. Ex vivo, EMPA improved baseline contractility and post-ischemic recovery of left ventricular pressure (dLVP from baseline: ~+4% in STZ+EMPA vs. -25% in STZ; ~+3% in EMPA vs. -28% in MIRI), enhanced coronary flow recovery, and reduced cardiac contracture, infarct size, and coronary LDH leakage in both diabetic and non-diabetic hearts. These effects may be associated with post-ischemic histological improvements, reduced vascular congestion, increased eNOS phosphorylation, activation of cardioprotective pathways, and inhibition of mPTP opening. Consistently, EMPA enhances wound healing and preserves eNOS phosphorylation in high-glucose (HG) human cardiac microvascular endothelial cells. In human cardiomyocytes, EMPA reduced hypoxia/reoxygenation (H/R) cell death, preserved nitrate and nitrite levels-effects abolished in the presence of L-NAME-and improved mitochondrial membrane potential in HG and/or H/R conditions. EMPA improved metabolic health and protected myocardial and coronary function likely via a permissive microvascular and myocardial phenotype that limits reperfusion injury, supporting its use against MIRI in normal and diabetic settings. - Source: PubMed
Publication date: 2026/04/17
Rocca CarmineDe Bartolo AnnaGranieri Maria ConcettaRago VittoriaConforti FrancescoUrlandini LidiaRomeo NaomiMattii LetiziaDe Caterina RaffaelePagliaro PasqualeAngelone TommasoPenna ClaudiaMadonna Rosalinda - Cerebral cavernous malformations (CCMs) are low-flow, thin-walled vascular conglomerates that arise within the central nervous system and constitute a significant cause of stroke. Experimental evidence indicates that mitochondrial dysfunction contributes to the pathogenesis of CCM, a disease that can be caused by PDCD10 deficiency. However, the specific mechanisms underlying mitochondrial homeostatic imbalance remain unclear. 3-oxoacid CoA-transferase 1 (OXCT1), localized in the mitochondrial matrix, serves as the rate-limiting enzyme of ketone body metabolism. Additionally, it also modulates diverse mitochondrial functions. Although the function of OXCT1 has been implicated in various diseases, its role in the progression of CCM awaits elucidation. Utilizing RNA-seq data from the CRISPR/Cas9-generated PDCD10-knockout endothelial cell line, primary endothelial cells from Pdcd10 mice, and CCM patient-derived endothelial cells, this study identified OXCT1 as a hub gene involved in mitochondrial pathways during CCM progression. Loss-of-function mutations of OXCT1 in malformed vascular endothelium accelerated disease progression and mediated mitochondrial impairment. High-throughput virtual screening identified S-adenosylmethionine (SAMe) as a small-molecule drug targeting the active site of OXCT1. Furthermore, SAMe is an orally available drug with high bioavailability and a favorable safety profile, which effectively suppressed disease progression in our murine model of CCM. In conclusion, this study provides initial evidence that OXCT1 is a novel therapeutic target in CCM and that SAMe holds promise as a potential treatment. - Source: PubMed
Publication date: 2026/03/21
Ye YongqingYan CongHuang XuyangHusilengtu Shi YucongLi YingZhao BonanDu WenzhongZhang DongdongXiong ZiyuMen ChunyangWang YuwenDuan QianpengBi RuiZhang YajieCheng JiaxinYang BaoSong ZheZhao XiaDu JiapeiShi Changbin - The ketogenic diet is a controversial approach to cancer therapy. Over 30% of hepatocellular carcinoma (HCC) cases harbor β-catenin activating mutations, among which the S33Y mutation represents a classical hotspot conferring constitutive pathway activation. Our previous metabolic profiling predicted that β-catenin-mutated HCC may exhibit intrinsic resistance to ketogenic therapy. 3-oxoacid CoA-transferase 1 (OXCT1), the key enzyme for ketone body catabolism, is aberrantly expressed in β-catenin-mutated HCC. This study explores how β-catenin-mutated HCC activates OXCT1 to reprogram ketone body metabolism to drive HCC ketogenic therapy resistance and metastasis. Utilizing subcutaneous tumor models and patient-derived xenograft (PDX) models of HCC, we demonstrated that ketogenic treatment was effective in β-catenin-wild-type HCC, whereas β-catenin-mutated HCC exhibited ketogenic therapy resistance and increased metastasis. Mechanistically, mutated β-catenin bound the transcription factor LEF1, which activated OXCT1 to promote ketolysis. An isotope metabolic flux experiment with C-labeled β-hydroxybutyrate confirmed that β-catenin-activated OXCT1 converts ketone bodies into glutamate. Blocking OXCT1 in β-catenin-mutated HCC abolished resistance to ketogenic therapy and reduced tumor glutamate levels. Furthermore, OXCT1, activated by mutated β-catenin, enhanced HCC metastasis via the p-STAT3 and epithelial-mesenchymal transition pathways. Inhibition of OXCT1 attenuated its promoting effect on metastasis. Overall, in β-catenin-mutated HCC, OXCT1 activation leads to metabolic reprogramming of ketone bodies, resulting in resistance to ketogenic therapy and promoting metastasis. Targeting OXCT1 represents a promising strategy for treating β-catenin-mutated HCC. - Source: PubMed
Publication date: 2026/03/09
Li HuanQian LiyuanJi YifanGeng YuanhaoLu YanjunZhang LaizhuXu YanchaoZong WeiweiJiang XiangZhou XianweiWen JingyuanLiu DonglinWang YeLi YunzhengLi BinghuaMa HuchengYu Decai - Ketone bodies have traditionally been recognized as glucose-sparing energy sources, with hepatic ketogenesis and peripheral ketolysis serving pivotal functions in maintaining energy homeostasis during fasting. Although they are commonly seen as harmful due to their link with ketoacidosis, recent studies emphasize their roles in organ protection. This has sparked interest in their possible use as a treatment for chronic kidney disease (CKD). In this study, we examined both exogenous and endogenous ketone body supplementation in adenine-induced kidney injury in mice. Supplementation with the ketone body precursor 1,3-butanediol significantly improved adenine-induced renal fibrosis, inflammation, and apoptotic cell death. However, genetically deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the key enzyme for ketogenesis, in the liver, kidney, or entire body, and removing Succinyl-CoA:3-ketoacid-CoA Transferase 1 (OXCT1), the enzyme for ketolysis, in the kidney alone, did not affect the severity of adenine-induced kidney damage. In contrast, the protective effects of 1,3-butanediol were partially diminished in mice with kidney-specific OXCT1 deficiency, indicating that OXCT1-mediated ketolysis is at least partly necessary for the renal protection afforded by exogenous ketone body supplementation. These findings suggest that supplementing with exogenous ketone bodies, rather than relying on endogenous hepatic or renal ketone production, protects the kidneys in adenine-induced kidney injury in mice, implying that local ketolysis within the kidney plays a mechanistic role in this protection. Our results highlight the therapeutic potential of exogenous ketone body administration in CKD and offer insights into how renal ketone metabolism helps protect against kidney injury. - Source: PubMed
Omachi ShojiSugahara ShoHoriguchi JunyaYasuda-Yamahara MakoKuwagata ShogoYamahara KosukeTanaka-Sasaki YukiIda ShogoKusaba TetsuroHumphreys Benjamin DKufukihara KenjiNakahara JinChin-Kanasaki MasamiKume Shinji