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Exercise and cardiac fibrosis 运动与心脏纤维化
IF 2.5 Q2 Medicine Pub Date : 2023-02-01 DOI: 10.1016/j.cophys.2022.100630
Kang Wang , Yawen Deng , Han Xiao

Cardiac fibrosis is an important pathological process leading to heart failure, characterized by the deposition of extracellular matrix proteins in the myocardial interstitium disrupting the normal structure and function of the myocardium. In this review, we summarized the underlying mechanisms by which exercise can exert cardioprotective effects by inhibiting cardiac fibrosis. In general, this review discussed that exercise promotes the secretion of cardioprotective exerkines, inhibits systemic activation of the renin–angiotensin system axis and sympathetic overactivation, attenuates oxidative stress and inflammatory responses, and regulates metabolism and noncoding RNA. In conclusion, our review may provide a current understanding of the mechanisms by which exercise acts as an important nonpharmacological strategy to intervene in cardiac fibrosis for cardioprotection.

心脏纤维化是导致心力衰竭的一个重要病理过程,其特征是细胞外基质蛋白沉积在心肌间质中,破坏心肌的正常结构和功能。在这篇综述中,我们总结了运动通过抑制心脏纤维化发挥心脏保护作用的潜在机制。总的来说,这篇综述讨论了运动促进心脏保护性运动因子的分泌,抑制肾素-血管紧张素系统轴的全身激活和交感过度激活,减轻氧化应激和炎症反应,并调节代谢和非编码RNA。总之,我们的综述可能提供了对运动作为一种重要的非药物策略干预心脏纤维化以保护心脏的机制的最新理解。
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引用次数: 0
Exercise counteracts vascular aging in long-term spaceflight: challenges and perspective 长期太空飞行中运动对抗血管老化:挑战与展望
IF 2.5 Q2 Medicine Pub Date : 2023-02-01 DOI: 10.1016/j.cophys.2022.100628
Tian Gao , Jing Huang , Xing Zhang , Feng Gao

Vascular aging, characterized by vascular wall thickening, collagen deposition, arterial stiffening, and endothelial dysfunction, is not necessarily determined chronologically, but can increase faster due to physical inactivity and other health risk factors. Astronauts exposed to microgravity and radiation during spaceflight undergo physiological changes associated with decrements in metabolic regulation, insulin signaling, endothelial homeostasis, and redox balance, which may foster aging features in the vasculature. Exercise has been proved an effective approach to mitigate microgravity-induced aging changes and thus protect vascular health. We here briefly review the mechanisms contributing to vascular aging changes in microgravity and exercise-afforded vasoprotection. Deep planetary exploration and longer space travel would impose unknown health risks, therefore, better understanding of exercise-induced health effects from an integrative perspective will help develop more efficient and effective exercise countermeasures.

以血管壁增厚、胶原沉积、动脉硬化和内皮功能障碍为特征的血管衰老不一定是按时间顺序确定的,但由于缺乏运动和其他健康危险因素,血管衰老的速度可能更快。宇航员在太空飞行中暴露在微重力和辐射下,会经历与代谢调节、胰岛素信号、内皮稳态和氧化还原平衡下降相关的生理变化,这可能会促进血管系统的衰老特征。运动已被证明是减轻微重力引起的衰老变化,从而保护血管健康的有效途径。我们在此简要回顾微重力和运动血管保护下血管老化变化的机制。深行星探索和更长时间的太空旅行将带来未知的健康风险,因此,从综合角度更好地了解运动引起的健康影响将有助于制定更高效和有效的运动对策。
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引用次数: 0
Physiological functions of mitophagy 线粒体自噬的生理功能
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100612
Milos Stanojlovic , Aniketh Bishnu , Francois Singh , Ian G Ganley

Mitochondria are vitally important organelles within our cells. In addition to being the key energy provider, they perform numerous other essential roles ranging from calcium homeostasis to iron metabolism. Therefore, these mitochondrial functions are dependent on the quality and number of mitochondria, which needs to be dynamic in response to a cell’s changing needs. Mitochondrial numbers themselves are controlled by mitochondrial biogenesis and turnover. Multiple pathways exist that result in the turnover of mitochondria, but the focus of this review will be on mitophagy (the autophagy of mitochondria). Here, we will touch on the basic mechanisms of mitophagy and how this has been translated from cell-based studies to complex mammalian systems. We will then examine the tasks that mitophagy serves in vivo. While mitochondrial quality control is a critical function of mitophagy, we will also discuss the recent roles that mitophagy plays in metabolic remodeling.

线粒体是我们细胞中至关重要的细胞器。除了作为主要的能量提供者外,它们还发挥着从钙稳态到铁代谢等许多其他重要作用。因此,这些线粒体功能依赖于线粒体的质量和数量,线粒体需要动态响应细胞不断变化的需求。线粒体数量本身受线粒体生物发生和周转的控制。线粒体的更新有多种途径,但本文将重点介绍线粒体的自噬。在这里,我们将探讨有丝自噬的基本机制,以及如何将其从基于细胞的研究转化为复杂的哺乳动物系统。然后我们将研究线粒体自噬在体内服务的任务。虽然线粒体质量控制是线粒体自噬的关键功能,但我们也将讨论线粒体自噬在代谢重塑中的最新作用。
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引用次数: 1
Chaperone-mediated autophagy: mechanisms and physiological relevance 伴侣介导的自噬:机制和生理相关性
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100597
Maryam Jafari , Mericka McCabe , Ana M Cuervo

A fraction of the cellular proteome can be selectively targeted to lysosomes for degradation within this organelle by a process known as chaperone-mediated autophagy (CMA). A dedicated network of genes and their protein products contribute to CMA execution and regulation. Here, we describe the most recent advances on the molecular dissection of CMA and on the understanding of the lysosomal and cellular components that contribute to its regulation, both under physiological conditions and in response to different stressors. The recent development of experimental mouse models to track, upregulate, or downregulate CMA in vivo has helped identify that, besides the role of CMA in cellular protein quality control, this type of autophagy also contributes to timely remodeling of the cellular functional proteome to modulate a variety of cellular processes. We review some of the novel regulatory roles of CMA and the consequences of CMA failure on physiology and cellular functioning.

细胞蛋白质组的一部分可以选择性地靶向溶酶体,通过称为伴侣介导的自噬(CMA)的过程在该细胞器内降解。基因及其蛋白质产物的专用网络有助于CMA的执行和调节。在这里,我们描述了CMA分子解剖的最新进展,以及对在生理条件下和对不同应激源的反应中参与其调节的溶酶体和细胞成分的理解。最近,在体内追踪、上调或下调CMA的实验小鼠模型的发展有助于发现,除了CMA在细胞蛋白质质量控制中的作用外,这种类型的自噬也有助于及时重塑细胞功能蛋白质组,以调节各种细胞过程。我们回顾了CMA的一些新的调节作用以及CMA失效对生理和细胞功能的影响。
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引用次数: 1
Role of autophagy in male and female fertility 自噬在男性和女性生育中的作用
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100611
Chao Liu , Bingbing Wu , Wenwen Liu , Wei Li

Autophagy is an important cellular homoeostatic process that transports cytoplasmic constituents to lysosomes and participates in various physiological processes. Recent findings have revealed novel functional roles of autophagy in the reproductive process, and dysfunctional autophagy has been reported to be associated with male and female infertility. In this review, we summarise the recent progress regarding autophagy in fertility and discuss important concerns in this field.

自噬是一种重要的细胞内平衡过程,它将细胞质成分运送到溶酶体,参与各种生理过程。最近的研究结果揭示了自噬在生殖过程中的新功能作用,自噬功能失调已被报道与男性和女性不育有关。本文综述了近年来自噬在生殖中的研究进展,并对该领域的重要问题进行了讨论。
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引用次数: 0
Recent insights concerning autophagy and endothelial cell nitric oxide generation 关于自噬和内皮细胞一氧化氮生成的最新见解
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100614
Seul-Ki Park , Jae Min Cho , Sohom Mookherjee , Paulo W. Pires , John David Symons

Although endothelial cell (EC) dysfunction contributes to the etiology of more diseases than any other tissue in the body, EC metabolism is an understudied therapeutic target. Evidence regarding the important role of autophagy in maintaining EC homeostasis is accumulating rapidly. Here, we focus on advances over the past two years regarding how EC autophagy mediates EC nitric oxide generation in the context of aging and cardiovascular complications, including coronary artery disease, aneurysm, and stroke. In addition, insight concerning the efficacy of maneuvers designed to boost EC autophagy in an effort to combat cardiovascular complications associated with repressed EC autophagy is discussed.

尽管内皮细胞(EC)功能障碍比体内任何其他组织都更能导致疾病的病因,但内皮细胞代谢是一个尚未得到充分研究的治疗靶点。关于自噬在维持EC稳态中的重要作用的证据正在迅速积累。在这里,我们关注过去两年关于EC自噬如何在衰老和心血管并发症(包括冠状动脉疾病、动脉瘤和中风)的背景下介导EC一氧化氮生成的进展。此外,还讨论了旨在促进EC自噬以对抗与抑制EC自噬相关的心血管并发症的策略的功效。
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引用次数: 0
Role of autophagy in liver diseases 自噬在肝脏疾病中的作用
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100594
Hideaki Morishita , Masaaki Komatsu

Since the initial discovery of autophagy in rat liver over 60 years ago, studies on hepatic autophagy have provided insight into the mechanisms and physiological functions of autophagy. These findings include the essential role of starvation-induced autophagy in supplying nutrients such as amino acids, glucose, and free fatty acids for energy production and the synthesis of macromolecules. Furthermore, it has been established that autophagy selectively degrades intracellular components such as p62/SQSTM1- and ubiquitin-containing droplets, as well as damaged organelles for intracellular quality control in hepatic cells. Dysfunction of hepatic autophagy can lead to several liver diseases, including hepatic tumors. In this review, we describe the physiological role of hepatic autophagy and its pathophysiological significance in several chronic liver disorders.

自60多年前首次发现大鼠肝脏自噬以来,对肝自噬的研究使人们对自噬的机制和生理功能有了更深入的了解。这些发现包括饥饿诱导的自噬在为能量生产和大分子合成提供氨基酸、葡萄糖和游离脂肪酸等营养物质方面的重要作用。此外,已经确定自噬选择性地降解细胞内组分,如p62/SQSTM1-和含泛素的液滴,以及用于胞内质量控制的受损细胞器。肝自噬功能障碍可导致多种肝脏疾病,包括肝肿瘤。本文就肝自噬在几种慢性肝脏疾病中的生理作用及其病理生理意义作一综述。
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引用次数: 0
Glycophagy — the physiological perspective on a newly characterized glycogen-selective autophagy 糖吞噬——一种新发现的糖原选择性自噬的生理学视角
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100598
Lea MD Delbridge , Parisa Koutsifeli , Sarah PT Fong , Marco Annandale , Kate L Weeks , James R Bell , Kimberley M Mellor

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently, a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein 1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that GABA Type A Receptor Protein Like 1 is primarily involved as the Atg8 family protein recruiting the Stbd1–glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation, and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

通过自噬降解细胞内成分是维持细胞完整性和稳态的基本过程。最近,一种糖原选择性自噬途径被描述为“糖吞噬”。糖原是葡萄糖可利用性的主要储存库和调节剂,糖吞噬是参与能量代谢的一个关键生理过程。糖吞噬介导的糖原降解似乎与糖原磷酸化酶的糖原分解的典型途径平行运作。有证据表明,淀粉结合域蛋白1 (Stbd1)是参与糖原糖吞噬标记的关键糖原结合蛋白,而GABA型a受体蛋白样1主要作为Atg8家族蛋白参与募集Stbd1 -糖原复合物形成糖原体。糖吞噬、蛋白质机制、调节和溶酶体葡萄糖释放的细微差别尚未完全阐明。在这篇小型综述中,我们批判性地分析了糖吞噬作为一种具有生理重要性的选择性自噬过程的现有证据基础,并强调了需要进一步研究的领域。
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引用次数: 0
Mechanisms and physiological functions of ER-phagy er吞噬的机制和生理功能
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100613
Pablo Sanz-Martinez, Alexandra Stolz

The endoplasmic reticulum (ER) is the largest cellular organelle that undergoes constant turnover upon diverse functional demands and cellular signals. Removal of nonfunctional or superfluous subdomains is balanced by the parallel expansion and formation of ER membranes, leading to the dynamic exchange of ER components. In recent years, selective autophagy of the ER, termed ER-phagy, has emerged as a predominant process involved in ER degradation and maintenance of ER homeostasis. Identification of multiple ER-phagy receptors, many with additional ER-shaping functions, paved the way for our molecular understanding of ER turnover in different cells and organs. In this review, we describe the molecular principles underling the physiological functions of ER-phagy in maintaining ER homeostasis via receptor-mediated macroautophagy and elaborate current focus points of the field.

内质网(ER)是最大的细胞器,根据不同的功能需求和细胞信号进行不断的更新。通过内质网膜的平行扩张和形成来平衡非功能性或多余的子结构域的去除,从而导致内质网成分的动态交换。近年来,内质网的选择性自噬被称为内质网吞噬,已成为内质网降解和维持内质网稳态的主要过程。多种ER吞噬受体的鉴定,其中许多具有额外的ER塑造功能,为我们了解不同细胞和器官中的ER转换分子铺平了道路。在这篇综述中,我们描述了内质网吞噬通过受体介导的巨噬维持内质网稳态的生理功能的分子原理,并阐述了目前该领域的热点。
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引用次数: 0
Role of autophagy in the eye: from physiology to disease 自噬在眼睛中的作用:从生理到疾病
IF 2.5 Q2 Medicine Pub Date : 2022-12-01 DOI: 10.1016/j.cophys.2022.100592
Hideaki Morishita

Autophagy is a conserved catabolic process that delivers cytoplasmic materials to the lysosome for degradation. Recent studies indicate that autophagy is essential for maintaining vision by regulating intracellular homeostasis in various structures of the eye, including the lens, retina, cornea, and trabecular meshwork. Dysregulated autophagy causes ocular diseases such as cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. Autophagy-independent degradation pathways such as LC3-associated phagocytosis in the retina and cytosolic PLAAT phospholipase-mediated organelle degradation in the lens are also physiologically important. Here, I summarize recent findings on the role of autophagy and related pathways in ocular physiology and disease.

自噬是一种保守的分解代谢过程,它将细胞质物质传递给溶酶体进行降解。最近的研究表明,自噬对维持视力至关重要,它通过调节眼睛各种结构的细胞内稳态,包括晶状体、视网膜、角膜和小梁网。失调的自噬导致白内障、青光眼、视网膜色素变性和老年性黄斑变性等眼部疾病。自噬不依赖的降解途径,如视网膜中lc3相关的吞噬和晶体中胞质PLAAT磷脂酶介导的细胞器降解,在生理上也很重要。在这里,我总结了自噬及其相关途径在眼部生理和疾病中的作用的最新发现。
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引用次数: 1
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Current Opinion in Physiology
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