Current Opinion in Physiology最新文献

Lipids are organic biomolecules that provide structural support to cells, but are also important for energy storage and signaling. Lipid profiling has emerged as a new technology with the potential of identifying new biomarkers and therapeutic targets. The lipid composition of cardiomyocyte membranes is altered during the process of cardiac remodeling, including exercise-induced heart enlargement (physiological cardiac hypertrophy) and disease-induced pathological remodeling. Phosphoinositide 3-kinase (PI3K) is an essential regulator of exercise-induced physiological hypertrophy and mediator of cardioprotection in cardiac stress settings. In this review, we first briefly summarize the protective role of exercise and PI3K on the heart. Next, we describe the regulation of lipids in the heart and circulation by exercise or transgenic expression of PI3K (increased or decreased), and contrast this to cardiac disease settings. We also describe studies in which exercise or PI3K-regulated lipids have been associated with cardiorespiratory fitness or cardioprotection, and discuss potential clinical applications.

Regular exercise improves cardiovascular and metabolic health. The beneficial effects of exercise are influenced by several factors, including exercise intensity, biological sex, and the time-of-day at which exercise is performed. In this short article, we review recent evidence of how exercise influences muscle metabolism and how circadian rhythm impacts tissue adaptations to exercise and exercise performance. Emerging out of these findings is a new appreciation for how nutrient timing and diurnal rhythms could be exploited to maximize the health benefits to exercise, while minimizing cardiovascular event risk.

Hair cells of the mammalian cochlea are specialized mechanosensory cells that convert mechanical stimuli into electrical signals to initiate the neuronal responses that lead to the perception of sound. The mechanoelectrical transduction (MET) machinery of cochlear hair cells is a multimeric protein complex that consists of the pore-forming subunits of the MET channel and several essential accessory subunits that are crucial to regulate channel function and render the channel mechanically sensitive. Mutations have been discovered in the genes that encode all known components of the MET machinery. These mutations cause hearing loss with or without vestibular dysfunction. Some mutations also affect other tissues such as the retina. In this brief review, we will summarize gene mutations that affect the MET machinery of hair cells and how the study of the affected genes has illuminated our understanding of the physiological role of the encoded proteins.

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.