Irisin protects against cerebral ischemia reperfusion injury in a SIRT3-dependent manner

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Cerebral ischemia-reperfusion (CIR) injury critically impacts stroke prognosis, yet effective therapeutic strategies remain limited. Irisin, an exercise-induced myokine, exhibits neuroprotective effects against cerebral ischemia. SIRT3, a mitochondrial deacetylase, is similarly implicated in mitigating injury. Given that irisin exerts protection via AMPK/PGC-1α pathway activation and SIRT3 acts downstream of PGC-1α , we hypothesized mediates irisin's neuroprotection CIR In vivo was modeled by inducing transient middle artery occlusion (MCAO) mice, while vitro conditions were replicated using oxygen-glucose deprivation (OGD) PC12 neuronal cultures. To elucidate the mechanistic role targeted interventions implemented: expression silenced transfection with small interfering RNA (siRNA), its enzymatic activity pharmacologically inhibited 3-TYP, selective inhibitor. Apoptotic systematically evaluated through TUNEL staining, Western blot analysis caspase-3, Bax Bcl-2. Oxidative stress parameters, including malondialdehyde (MDA) levels glutathione (GSH) content, measured colorimetric assays. Neurological function mice quantified modified Severity Score (mNSS). Our results demonstrated mitigates apoptosis oxidative dose-dependently activating signaling. At optimal dosage, effectively restored levels, reduced damage, improved neurological recovery models. Notably, significantly attenuated specific Further validation experiments revealed overexpression synergistically enhanced irisin-mediated OGD-induced injury, whereas knockout substantially diminished efficacy. data shown exerted protective at least part, activation. This study establishes irisin/SIRT3 as novel target for ischemic stroke, providing insights future interventions.

Language: Английский

Molecular Insights into Oxidative-Stress-Mediated Cardiomyopathy and Potential Therapeutic Strategies

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 670 - 670

Published: May 6, 2025

Cardiomyopathies comprise a heterogeneous group of cardiac disorders characterized by structural and functional abnormalities in the absence significant coronary artery disease, hypertension, valvular or congenital defects. Major subtypes include hypertrophic, dilated, arrhythmogenic, stress-induced cardiomyopathies. Oxidative stress (OS), resulting from an imbalance between reactive oxygen species (ROS) production antioxidant defenses, has emerged as key contributor to pathogenesis these conditions. ROS-mediated injury drives inflammation, protease activation, mitochondrial dysfunction, cardiomyocyte damage, thereby promoting remodeling decline. Although numerous studies implicate OS cardiomyopathy progression, precise molecular mechanisms remain incompletely defined. This review provides updated synthesis current findings on OS-related signaling pathways across subtypes, emphasizing emerging therapeutic targets within redox-regulatory networks. A deeper understanding may guide development targeted strategies improve clinical outcomes affected patients.

Language: Английский