Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

Hyatt, Hayden W.; Özdemir, Merve; Yoshihara, Toshinori; Nguyen, Branden L.; Deminice, Rafael; Powers, Scott K.

doi:10.1016/j.redox.2020.101802

Cited by 25 publications

(33 citation statements)

References 72 publications

(109 reference statements)

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“…Specifically, oxidative stress can elevate proteolysis in three independent ways. First, oxidative stress often results in increased cytosolic free calcium, and elevated cytosolic calcium can activate both calpains and caspase-3 [ 19 , 20 , 37 , 38 ]. Second, redox disturbances can stimulate several transcriptional activators that promote expression of genes involved in proteolysis (i.e., atrogenes) [ 39 , 40 ].…”

Section: Signaling Links Between Mitochondrial Dysfunction and Skeletal Muscle Wastingmentioning

confidence: 99%

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Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Hyatt

Powers

2021

Antioxidants

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Skeletal muscle is the most abundant tissue in the body and is required for numerous vital functions, including breathing and locomotion. Notably, deterioration of skeletal muscle mass is also highly correlated to mortality in patients suffering from chronic diseases (e.g., cancer). Numerous conditions can promote skeletal muscle wasting, including several chronic diseases, cancer chemotherapy, aging, and prolonged inactivity. Although the mechanisms responsible for this loss of muscle mass is multifactorial, mitochondrial dysfunction is predicted to be a major contributor to muscle wasting in various conditions. This systematic review will highlight the biochemical pathways that have been shown to link mitochondrial dysfunction to skeletal muscle wasting. Importantly, we will discuss the experimental evidence that connects mitochondrial dysfunction to muscle wasting in specific diseases (i.e., cancer and sepsis), aging, cancer chemotherapy, and prolonged muscle inactivity (e.g., limb immobilization). Finally, in hopes of stimulating future research, we conclude with a discussion of important future directions for research in the field of muscle wasting.

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Section: Signaling Links Between Mitochondrial Dysfunction and Skeletal Muscle Wastingmentioning

confidence: 99%

“…Calpains are calcium-activated proteases that selectively cleave target proteins [ 19 , 20 ]. Calpain activation occurs due to increased cytosolic levels of free calcium and oxidative stress is an established trigger to promote disturbances in cellular calcium homeostasis [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Hyatt

Powers

2021

Antioxidants

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“…For example, ROS have been shown to accumulate by 4-7-fold in tibialis anterior muscle over the course of 3-21 days following denervation, leading to a reduction in muscle mass by 21 days [90]. Similar reductions in CSA and muscle weight have been observed after mechanical ventilation [103,128], hindlimb unloading [72,73] and denervation [51], with corresponding reductions in force production [103]. With chronic muscle disuse, release of H 2 O 2 stimulates AMPK-mediated proteolytic pathways, including the ubiquitin-proteosome and autophagy-lysosome systems, leading to increased muscle protein degradation and fiber atrophy [99,103,128,130].…”

Section: Mitochondrial Ros Production and Ca 2+ Homeostaismentioning

confidence: 78%

“…In addition, chronic muscle disuse exerts a profound influence on mitochondrial morphology and dynamics by altering the fission/fusion regulatory protein balance. The levels of fission proteins, Drp1 and Fis1, remain elevated relative to fusion proteins, Opa1 and Mfn1, thus promoting a more fragmented mitochondrial network [ 86 , 88 , 97 , 98 , 100 , 101 , 102 , 103 ]. The consequence of this altered regulatory protein expression is evidenced by altered organelle morphology with disuse.…”

Section: Molecular Basis Of Mitochondrial Decline During Disusementioning

confidence: 99%

“…Although IMF mitochondria elicit greater absolute rates of respiration, SS mitochondria are more malleable, displaying ~45% reductions in oxygen consumption as compared to ~16% declines observed in the IMF fraction three days post-denervation. In fact, mitochondrial deficits are evident after just 12 h of machine-supported ventilation, evidenced by declines in respiration along with reductions in the respiratory control ratio (RCR), which signifies uncoupling of ATP production from electron flow [ 103 , 127 , 128 ]. These data indicate that mitochondrial dysfunction is an early event brought about by muscle inactivity.…”

Section: Functional Consequences Of Muscle Disusementioning

confidence: 99%

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Mitochondrial Bioenergetics and Turnover during Chronic Muscle Disuse

Memme

Slavin

Moradi

et al. 2021

IJMS

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Periods of muscle disuse promote marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. Thus, understanding the molecular underpinnings of muscle mitochondrial decline with prolonged inactivity is of considerable interest. There are translational applications to patients subjected to limb immobilization following injury, illness-induced bed rest, neuropathies, and even microgravity. Studies in these patients, as well as on various pre-clinical rodent models have elucidated the pathways involved in mitochondrial quality control, such as mitochondrial biogenesis, mitophagy, fission and fusion, and the corresponding mitochondrial derangements that underlie the muscle atrophy that ensues from inactivity. Defective organelles display altered respiratory function concurrent with increased accumulation of reactive oxygen species, which exacerbate myofiber atrophy via degradative pathways. The preservation of muscle quality and function is critical for maintaining mobility throughout the lifespan, and for the prevention of inactivity-related diseases. Exercise training is effective in preserving muscle mass by promoting favourable mitochondrial adaptations that offset the mitochondrial dysfunction, which contributes to the declines in muscle and whole-body metabolic health. This highlights the need for further investigation of the mechanisms in which mitochondria contribute to disuse-induced atrophy, as well as the specific molecular targets that can be exploited therapeutically.

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Effect of dietary fiber on gut barrier function, gut microbiota, short‐chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta‐analysis

Liu

Wang

et al. 2022

J Parenter Enteral Nutr

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Background: Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota, and clinical outcomes in critically ill patients, the results were not consistent. Objective:The purpose was to explore the effect of DF on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation, and clinical outcomes in critically ill patients. Methods:A search was performed through five databases from inception to July 12, 2021. Data were expressed as mean difference (MD) or odds ratio (OR) with CI.Results: Twenty-one studies involving 2084 critically ill patients were included.There was a significant reduction in intestinal permeability, demonstrated by lactulose/rhamnose ratio (MD, −0.04; 95% CI, −0.08 to −0.00; P = 0.03) on day 8, Creactive protein on day 14 (MD, −36.66; 95% CI, −44.40 to −28.93; P < 0.001) and duration of hospital stay (MD, −3.16; 95% CI, −5.82 to −0.49; P < 0.05) after DF supplement. There were no significant differences in SCFA levels, duration of mechanical ventilation, and mortality between two groups. However, subgroup analysis results indicated significant decreases in duration of hospital stay and risk of mortality were seen in the subgroups with a supplementary fiber dose ≥20 g/day (MD, −5.62 [95% CI, −8.04 to −3.21; P < 0.0001]; OR, 0.18 [95% CI, 0.06-0.57; P = 0.004]), as well as in the medical intensive care unit (MD, −4.77 [95% CI, −7.48 to −2.07; P < 0.01]; OR, 0.13 [95% CI, 0.03-0.65; P < 0.05]). Conclusions: DF may improve gut barrier function, modulate intestinal microbiota, decrease systemic inflammatory response, and advance clinical outcomes in critically ill patients.

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Calpains play an essential role in mechanical ventilation-induced diaphragmatic weakness and mitochondrial dysfunction

Cited by 25 publications

References 72 publications

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Mitochondrial Bioenergetics and Turnover during Chronic Muscle Disuse

Effect of dietary fiber on gut barrier function, gut microbiota, short‐chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta‐analysis

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