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Autophagy in the Heart

机译:心中的自噬

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The autophagic machinery is a well-conserved degradation system in eukaryotes from yeast to mammals. Autophagy has been thought of as a nonselective degradation process in which cytoplasmic proteins and organelles are degraded by fusion with lysosome. Recent studies have revealed selective forms of autophagy, such as mitochondria-specific autophagy, termed “mitophagy”. Research over the past decade has revealed that autophagy in cardiomyocytes plays a protective role, not only during hemodynamic stress but in homeostasis during aging. Hemodynamic stress and aging induce mitochondrial damage, leading to increased oxidative stress and decreased ATP production. Damaged mitochondria are generally degraded through mitophagy, which might be the main protective function of autophagy in the heart. Complete digestion of mitochondrial DNA through mitophagy is important to avoid inflammatory responses that can induce heart failure. A polyamine, spermidine, is reported to bring about an extension of lifespan and to protect the heart from age-related cardiac dysfunction, both of which are mediated through induction of autophagy. Therefore, appropriate induction of autophagy could be a novel therapeutic target for cardiovascular diseases, including heart failure. However, precise evaluation of autophagic activity in the human heart is difficult at this time, but exploitation of the novel technique of autophagy evaluation is expected for both drug discovery and clinical application.
机译:自噬机制是从酵母到哺乳动物的真核生物中保存完好的降解系统。自噬被认为是非选择性降解过程,其中通过与溶酶体融合来降解细胞质蛋白和细胞器。最近的研究表明自噬的选择性形式,例如线粒体特异的自噬,称为“有丝分裂”。过去十年的研究表明,心肌细胞的自噬不仅在血流动力学压力期间,而且在衰老过程中的稳态中都起保护作用。血液动力学压力和衰老引起线粒体损伤,导致氧化应激增加和ATP产生减少。线粒体受损通常通过线粒体降解,这可能是心脏自噬的主要保护功能。通过线粒体完全消化线粒体DNA对于避免可引起心力衰竭的炎症反应很重要。据报道,多胺亚精胺可延长寿命并保护心脏免受年龄相关的心脏功能障碍的影响,两者均通过诱导自噬而介导。因此,适当的自噬诱导可能是包括心力衰竭在内的心血管疾病的新治疗靶标。但是,此时很难精确评估人心脏中的自噬活性,但是对于药物发现和临床应用都期望开发新的自噬评估技术。

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