Differentiation, Journal Year: 2024, Volume and Issue: 141, P. 100829 - 100829
Published: Dec. 5, 2024
Language: Английский
Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)
Published: Feb. 11, 2025
Carnitine palmitoyltransferase 1A (CPT1A), a succinylating enzyme, is highly expressed in various malignant tumors and promotes tumor progression. Succinylation posttranslational modification that has been reported diseases, but its role NK/T-Cell lymphoma nasal type (ENKTL-NT) remains underexplored. In this study, bioinformatics analysis showed glycolytic major metabolic pathway ENKTL-NT as the expression of many related kinases are increased. CPT1A probably mediates process, indicated by GO-enrichment analysis. Studies was upregulated tissues, high associated with poor prognosis ENKTL-NT. promoted proliferation, colony formation, invasion process cells suppresses apoptosis. Mechanistically, succinylation LDHA at lysine 318 (K318), which increase protein stability final level LDHA. Both knockdown mutation (K318R) abolished cancer-promoting effects all, study reveals mechanism underlying via inducing reprogramming These findings might provide potential targets for diagnosis or therapy
Language: Английский
Citations
0
Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 17, 2025
Abstract The long-term outlook for patients grappling with lung cancer (LC) remains bleak, adenocarcinoma (LUAD) emerging as the most predominant histological subtype. Our Mendelian randomization (MR) investigation spotlighted that heightened levels of circulating protein serpin peptidase inhibitor family G1 (SERPING1) substantially mitigated LC risk. fusion multi-omics strategies unveiled SERPING1 exhibited diminished expression in LUAD compared to healthy individuals both tissues and serum, showcasing elevated demonstrating improved prognoses. Furthermore, a robust correlation efficacy immunotherapy. Through meticulous vivo vitro analyses, we unraveled impeded proliferation, migration, invasion wound healing cells via tuberous sclerosis 2 (TSC2)/mammalian target rapamycin (mTOR) pathway. Mechanistically, WNT inhibitor- Specificity Protein (SP5) was delineated facilitator transcription by binding gene promoter. Intriguingly, aside from association between systolic blood pressure, glycosylated hemoglobin (HbA1c), type I diabetes, no discernible link overexpression risks other cardiometabolic conditions diseases evident. In summary, emerges novel tumor suppressor SP5/SERPING1/TSC2 is promising therapeutic context LUAD.
Language: Английский
Citations
0
Pharmacological Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 100051 - 100051
Published: Feb. 1, 2025
The carnitine palmitoyltransferases (CPTs) play a key role in controlling the oxidation of long-chain fatty acids and are potential therapeutic targets for diseases with strong metabolic component, such as obesity, diabetes, cancer. Four distinct proteins CPT1A, CPT1B, CPT1C, CPT2, differing tissue expression catalytic activity. CPT1s finely regulated by malonyl-CoA, metabolite whose intracellular levels reflect cell's nutritional state. Although CPT1C does not exhibit significant activity, it is capable modulating functioning other neuronal proteins. Structurally, all CPTs share Y-shaped tunnel that allows entry 2 substrates accommodation acyl group hydrophobic pocket. Several molecules targeting these enzymes have been described, some showing normalizing blood glucose diabetic patients, others that, through central mechanism, anorexigenic enhance energy expenditure. However, given critical roles certain tissues, heart, liver, brain, essential to fully understand differences between various isoforms. We analyze detail structure proteins, their cellular physiological functions, also describe drugs identified date having inhibitory or activating capabilities This knowledge will support design new specific each isoform, development nanomedicines can selectively target particular tissues cells. SIGNIFICANCE STATEMENT: Carnitine palmitoyltransferase (CPT) gatekeepers acid oxidation, great pharmacological treat like In recent years, progress has made understanding 3-dimensional pathophysiological functions. A deeper CPT family members enable selective approaches fewer side effects.
Language: Английский
Citations
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Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)
Published: March 1, 2025
ABSTRACT Bone marrow mesenchymal stem cells (BM‐MSCs) have promising prospects in bone repair and regenerative medicine. However, BM‐MSCs gradually lose their original pluripotency differentiation potential after successive passages. This study aimed to reveal the mechanism underlying phenomenon. Western blotting, SA‐β‐gal staining Alizarin red were used evaluate senescence phenotype osteogenic ability. Mitochondrial ROS levels detected using flow cytometry. Protein interactions succinylation modifications identified by Co‐IP assays. With increase passage times, proliferation of weakened, expression level CPT1A was decreased. with fewer passages (P1–P5 generations) showed increased mitochondrial production reduced enzyme activity superoxide dismutase 2 (SOD2) knockdown CPT1A. In contrast, overexpression multiple‐round‐passed (P10–P15 has opposite effect. Therefore, is associated ageing phenotypes capacity BM‐MSCs. Knocking down significantly modification SOD2, resulting a decrease SOD2 mitochondria. Overexpression enhanced at key site K130, thereby reducing cell promoting differentiation. this boosting effect reversed when mutation occurred K130 SOD2. promotes (K130) induce accumulation mitochondria activity, which alleviates BM‐MSC enhances
Language: Английский
Citations
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Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111744 - 111744
Published: March 1, 2025
Language: Английский
Citations
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Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
Language: Английский
Citations
0
Differentiation, Journal Year: 2024, Volume and Issue: 141, P. 100829 - 100829
Published: Dec. 5, 2024
Language: Английский
Citations
0