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心肌细胞稳态、衰老及病理过程中的自噬

Autophagy in cardiac myocyte homeostasis, aging, and pathology.

作者信息

Terman Alexei, Brunk Ulf T

机构信息

Division of Experimental Pathology, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.

出版信息

Cardiovasc Res. 2005 Dec 1;68(3):355-65. doi: 10.1016/j.cardiores.2005.08.014. Epub 2005 Oct 6.

Abstract

Autophagy, an intralysosomal degradation of cells' own constituents that includes macro-, micro-, and chaperone-mediated autophagy, plays an important role in the renewal of cardiac myocytes. This cell type is represented by long-lived postmitotic cells with very poor (if any) replacement through differentiation of stem cells. Macroautophagy, the most universal form of autophagy, is responsible for the degradation of various macromolecules and organelles including mitochondria and is activated in response to stress, promoting cell survival. This process is also involved in programmed cell death when injury is irreversible. Even under normal conditions, autophagy is somewhat imperfect, underlying gradual accumulation of defective mitochondria and lipofuscin granules within aging cardiac myocytes. Autophagy is involved in the most important cardiac pathologies including myocardial hypertrophy, cardiomyopathies, and ischemic heart disease, a fact that has led to increasing attention to this process.

摘要

自噬是细胞内对自身成分的溶酶体降解过程,包括巨自噬、微自噬和伴侣介导的自噬,在心肌细胞更新中起重要作用。这种细胞类型以长寿命的终末分化细胞为代表,通过干细胞分化进行替换的能力非常弱(如果有的话)。巨自噬是自噬最普遍的形式,负责降解包括线粒体在内的各种大分子和细胞器,并在应激反应中被激活,促进细胞存活。当损伤不可逆时,这个过程也参与程序性细胞死亡。即使在正常条件下,自噬也存在一定缺陷,这是衰老心肌细胞内有缺陷的线粒体和脂褐素颗粒逐渐积累的原因。自噬参与了包括心肌肥大、心肌病和缺血性心脏病在内的最重要的心脏疾病,这一事实导致人们对这一过程的关注日益增加。

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