ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence

Autophagy, Год журнала: 2024, Номер 20(9), С. 2000 - 2016

Опубликована: Май 18, 2024

Bleomycin exhibits effective chemotherapeutic activity against multiple types of tumors, and also induces various side effects, such as pulmonary fibrosis neuronal defects, which limit the clinical application this drug. Macroautophagy/autophagy has been recently reported to be involved in functions bleomycin, yet mechanisms their crosstalk remain insufficiently understood. Here, we demonstrated that reactive oxygen species (ROS) produced during bleomycin activation hampered autophagy flux by inducing lysosomal membrane permeabilization (LMP) obstructing degradation. Exhaustion ROS with N-acetylcysteine relieved LMP defects. Notably, observed blockage preceded emergence cellular senescence treatment. In addition, promoting or inhibiting autophagy-lysosome degradation alleviated exacerbated phenotypes senescence, respectively. This suggests alternation is more a regulatory mechanism than consequence bleomycin-induced senescence. Taken together, reveal specific role mediating defects autophagic further regulating vitro vivo. Our findings, conversely, indicate pathway target for modulating bleomycin. These provide new perspective optimizing clinically applicable chemotherapeutics devoid severe side-effects.

Язык: Английский

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Cellular reprogramming as a tool to model human aging in a dish

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 28, 2024

Abstract The design of human model systems is highly relevant to unveil the underlying mechanisms aging and provide insights on potential interventions extend health life span. In this perspective, we explore 2D or 3D culture models comprising induced pluripotent stem cells transdifferentiated obtained from aged age-related disorder-affected donors enhance our understanding catalyze discovery anti-aging interventions.

Язык: Английский

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Advances in the molecular mechanisms of statins in regulating endothelial nitric oxide bioavailability: Interlocking biology between eNOS activity and L-arginine metabolism

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116192 - 116192

Опубликована: Янв. 22, 2024

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested reduce the risk cardiovascular events owing their pleiotropic effects on vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition smooth muscle cell proliferation. The major beneficial effect in maintaining homeostasis is induction nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) cells. mechanisms underlying increased eNOS activation well-established various fields, transcriptional post-transcriptional regulation, kinase-dependent phosphorylation protein-protein interactions. However, mechanism which affect metabolism L-arginine, a precursor biosynthesis, has rarely discussed. Autophagy, crucial for energy homeostasis, regulates functions, production angiogenesis, potential therapeutic target diseases. this review, addition summarizing molecular statins, we also discuss L-arginine.

Язык: Английский

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Association between systemic immune inflammation index and cataract incidence from 2005 to 2008

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 2, 2025

Язык: Английский

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Beyond the Hayflick limit: How microbes influence cellular aging

Ageing Research Reviews, Год журнала: 2025, Номер 104, С. 102657 - 102657

Опубликована: Янв. 7, 2025

Язык: Английский

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