Mitochondria-associated membranes (MAMs) in age-related heart diseases, role of endoplasmic reticulum stress

Advances in pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Causal role of mitochondrial proteins in aortic aneurysms: Evidence from Mendelian randomization, transcriptomic analysis, and experimental validation

Medicine, Journal Year: 2025, Volume and Issue: 104(10), P. e41757 - e41757

Published: March 7, 2025

Mitochondrial dysfunction has been implicated in the pathogenesis of aortic aneurysms (AA); however, causal role mitochondrial-related proteins remains unclear. This study employs a Mendelian randomization (MR) approach to investigate potential relationship between mitochondrial and AA. Genetic instruments for were obtained from IEU Open genome-wide association database, while AA-related genetic data sourced FinnGen biobank. Inverse-variance weighting (IVW) served as primary MR method, with MR-Egger weighted median approaches utilized complementary methods. Sensitivity analyses, including Cochran Q test, intercept, MR-PRESSO, performed assess heterogeneity pleiotropy. Reverse analysis was conducted exclude possibility reverse causation. To enhance robustness findings, replication carried out using Catalog data, meta-analysis by integrating discovery datasets. Gene expression validation Expression Omnibus dataset, gene set enrichment (GSEA) applied explore relevant biological pathways. Additionally, vitro experiments employing platelet-derived growth factor-BB-induced human smooth muscle cells validate patterns at both mRNA protein levels. Through rigorous variant selection, IVW, sensitivity replication, meta-analysis, we identified iron-sulfur cluster assembly enzyme (ISCU), 39S ribosomal L14 (MRPL14), peptide methionine sulfoxide reductase (MSRA) associated analyses confirmed these no evidence or ruled demonstrated that ISCU significantly upregulated, whereas MRPL14 MSRA downregulated AA tissues. GSEA revealed are involved pathways related inflammation, immune response, vascular remodeling. In further corroborated demonstrating consistent cells. provides robust experimental supporting ISCU, MRPL14, pathogenesis. These may serve biomarkers therapeutic targets AA, warranting investigation.

Language: Английский

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Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia–Reperfusion Injury

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 340 - 340

Published: March 14, 2025

Delayed reperfusion of the ischemic heart (I/R) is known to impair recovery cardiac function and produce a wide variety myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation proteases, changes in gene expression. Although I/R injury has been reported induce formation reactive oxygen species (ROS), inflammation, intracellular Ca2+ overload, generation oxidative stress considered play critical role development dysfunction. Increases production superoxide, hydroxyl radicals, oxidants, such as hydrogen peroxide hypochlorous acid, occur hearts subjected injury. In fact, mitochondria are major source excessive ROS due impairment electron transport system well xanthine oxidase NADPH oxidase. Nitric oxide synthase, mainly present endothelium, also activated injury, leading nitric oxide, which, upon combination with superoxide generates nitrosative stress. Alterations function, sarcolemma, sarcoplasmic reticulum activities, mitochondrial phosphorylation, protease simulated exposing oxyradical-generating (xanthine plus oxidase) or H2O2. On other hand, endogenous antioxidants dismutase, catalase, glutathione peroxidase, concentration transcription factor (Nrf2), which modulates expression various antioxidants, depressed hearts. Furthermore, pretreatment catalase N-acetylcysteine, mercaptopropionylglycerine observed attenuate I/R-induced handling Ca2+-regulatory activities; additionally, it found depress improve function. These observations indicate that intimately involved pathological effects different alterations Thus, we faced task developing safe effective agents for upregulating therapy

Language: Английский

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Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 679 - 679

Published: May 8, 2025

Dynamin-related protein 1 (Drp1) is a crucial player in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), lipid droplets (LDs) are fundamental for metabolism. This study utilized liver-specific Drp1 knockout (Drp1LiKO) mice to investigate the effects of deficiency on organelle interactions, metabolism, inflammation. Our analysis revealed disrupted mitochondria LDs, as well altered among ER, LDs Drp1LiKO mice. Through mass spectrometry microarray analysis, we identified changes profiles perturbed expression metabolism genes livers Further vitro experiments using primary hepatocytes from confirmed disturbances increased These findings highlight critical involvement regulating efficient overall health. Targeting Drp1-mediated may offer potential developing therapies diseases associated with

Language: Английский

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New insights into the relationship of mitochondrial metabolism and atherosclerosis

Cellular Signalling, Journal Year: 2024, Volume and Issue: 127, P. 111580 - 111580

Published: Dec. 27, 2024

Language: Английский

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