Current Opinion in Physiology最新文献

Cardiomyocyte Ca²⁺ dictates cardiac contraction via excitation–contraction coupling (ECC) and excitation–transcription coupling. Adaptation to these processes also majorly contributes to enhanced contractile function and capacity following exercise training. Cytoplasmic Ca²⁺ release controls sarcomeric contraction, with important modulation by the voltage-sensitive plasma membrane L-type Ca²⁺ channel and the Ryanodine receptor, as well as the sarcoplasmic reticulum Ca²⁺ ATPase. Exercise training increases and enhances these ECC subprocesses, in a manner that increases and enhances cardiac contraction. Also, adaptation to exercise training further includes myofilament Ca²⁺ sensitization. Then, there are several aspects linked to postexercise training cardiomyocyte Ca²⁺ handling that remains speculative and inconclusive, but could if proven true to be of special importance. This includes Ca²⁺-linked muscle-specific gene transcription to alter cell architecture and size, and it includes the scenario whereby Ca²⁺ cycling and adaptations may alter arrhythmogenicity. These aspects of cardiac Ca²⁺ adaptations to exercise training are discussed in this review article.

Exercise, effectively and safely, contributes to the rehabilitation of the ischemic heart. In the field of cardiovascular health, it has attracted increasing attention because of lower cost and fewer side effects. Mechanisms of exercise in prevention and treatment of ischemic heart disease (IHD) involve the regulation of mitophagy, oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and cardiac pathological remodeling through exerkines and gut microbiomes. To provide theoretical basis and ideas for the prevention and postoperative rehabilitation of IHD, we summarized and discussed the latest progress and future development of the above mechanisms.

Cardiac troponins (cTn) are proteins that regulate cardiomyocyte contraction. A rise and fall of cTn above the upper reference limit is diagnostic of myocardial injury. Therefore, cTn measurements are part of the routine workup when suspecting acute coronary syndromes.

Exercise can also produce cTn elevations. Many studies in the last three decades have advanced our understanding of exercise-induced cTn release. Beyond technical improvements in cTn assays, various predictors of cTn release have been identified, whereas insight into exercise-induced cTn release patterns and its clinical implications have been improved. Whether cTn release in athletes represents a physiological or pathological response remains a topic of debate. This review summarizes our current understanding of exercise-induced cTn release and provides directions for future studies. We address how to 1) discriminate physiological versus pathological cTn release, 2) unravel the underlying mechanisms of exercise-induced cTn release, and 3) determine whether exercise-induced cTn elevation is a novel cardiovascular risk factor.

PIEZO1 and PIEZO2 are mechanically gated ion channels that confer mechanosensitivity to a variety of cell types and are thus essential for numerous physiological processes, including touch, pain, blood-pressure regulation, cell migration, or immune function. Recently published cryo-electron microscopy structures of PIEZO1 and PIEZO2 have enabled the structure-guided examination of PIEZO channel function, which has significantly improved our understanding of the cellular and molecular mechanisms underlying the mechanogating of PIEZOs. Here, we summarize evidence suggesting that forces acting in and on cells are transmitted to PIEZOs via both membrane tension (force-from-lipids) and by cytoskeletal strain (force-from-filament) and propose that the two force-transmission pathways act in parallel or synergistically to activate PIEZOs. Moreover, we discuss the role of different protein domains in the detection of mechanical forces from different origins and propose that PIEZOs are polymodal mechanosensors that detect different types of mechanical stimuli via different intramolecular force-coupling mechanisms.

The drug-resistance crisis has become dire and new antibiotic targets and strategies are required. Mechanosensitive channel of large conductance (MscL) is a conserved bacterial mechanosensitive channel that plays the role of ‘osmotic-emergency-release-valve. It has the largest-gated pore known allowing osmoprotectants out, and other compounds into the cell. Inappropriate gating of the channel can lead to slow growth, decreased viability, and an increase in potency for many antibiotics. The ‘membrane permeability’ observed for some antibiotics, including streptomycin, is mediated by directly binding to and activating MscL. Novel compounds that are MscL agonists have also recently been isolated. Although the compounds are diverse, the binding sites of all characterized MscL-specific agonists are within the same general region of the MscL complex, leading to an in silico screening for compounds that bind this region. In sum, these studies demonstrate that MscL is a viable drug target that may lead to a new generation of antibiotics and adjuvants.

Exercise leads to numerous beneficial whole-body effects and can protect against the development of obesity, cardiometabolic, and neurodegenerative diseases. Recent studies have highlighted the importance of inter-tissue crosstalk with a focus on secretory factors that mediate communication among organs, including adipose tissue and the heart. Studies investigating the effects of exercise on brown adipose tissue (BAT) and white adipose tissue (WAT) demonstrated that adipokines are released in response to exercise and act on the heart to decrease inflammation, alter gene expression, increase angiogenesis, and improve cardiac function. This review discusses the exercise-induced adaptations to BAT and WAT and how these adaptations affect heart health and function, while highlighting the importance of tissue crosstalk.

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.

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.

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.

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.