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心肌细胞自噬与癌症化疗

Cardiomyocyte autophagy and cancer chemotherapy.

作者信息

Li Dan L, Hill Joseph A

机构信息

Department of Internal Medicine Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Department of Internal Medicine Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

出版信息

J Mol Cell Cardiol. 2014 Jun;71:54-61. doi: 10.1016/j.yjmcc.2013.11.007. Epub 2013 Nov 14.

Abstract

Autophagy, an evolutionally conserved process of controlled cellular cannibalization, plays a vital role in cardiac physiology. Perturbations in cardiomyocyte autophagy contribute to the pathogenesis of a wide range of cardiac diseases, many of which culminate in heart failure. With recent advances in cancer chemotherapy and consequent improvements in cancer survival, drug-induced toxicity to the heart has assumed greater importance. As a number of prominent cellular pathways are critical to the survival of both tumor cells and heart cells, it comes as little surprise that therapies targeting those pathways have consequences in both tissues. Little is known presently about cardiomyocyte autophagy, a prominent cellular response to stress, in the setting of chemotherapy, but preliminary evidence suggests an important and context-dependent role. Dissecting the role of autophagy in "onco-cardiology" will likely yield insights into mechanisms underlying cardiomyopathy and may lead to novel means to protect the myocardium from chemotherapy-induced injury. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".

摘要

自噬是一种进化上保守的、受调控的细胞自我吞噬过程,在心脏生理学中起着至关重要的作用。心肌细胞自噬的紊乱会导致多种心脏疾病的发病机制,其中许多最终会导致心力衰竭。随着癌症化疗的最新进展以及癌症生存率的相应提高,药物对心脏的毒性变得更加重要。由于许多重要的细胞途径对肿瘤细胞和心脏细胞的存活都至关重要,因此针对这些途径的疗法在两种组织中都会产生影响也就不足为奇了。目前对于化疗背景下心肌细胞自噬(一种对压力的显著细胞反应)了解甚少,但初步证据表明其具有重要且依赖于背景的作用。剖析自噬在“肿瘤心脏病学”中的作用可能会深入了解心肌病的潜在机制,并可能导致保护心肌免受化疗诱导损伤的新方法。本文是名为“蛋白质质量控制、泛素蛋白酶体系统和自噬”的特刊的一部分。

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