Mechanisms by which hydrogen sulfide attenuates muscle function following ischemia–reperfusion injury: effects on Akt signaling, mitochondrial function, and apoptosis

Abstract

Ischemia–reperfusion injury is caused by a period of ischemia followed by massive blood flow into a tissue that had experienced restricted blood flow. The severity of the injury is dependent on the time the tissue was restricted from blood flow, becoming more severe after longer ischemia times. This can lead to many complications such as tissue necrosis, cellular apoptosis, inflammation, metabolic and mitochondrial dysfunction, and even organ failure. One of the emerging therapies to combat ischemic reperfusion injury complications is hydrogen sulfide, which is a gasotransmitter that diffuses across cell membranes to exert effects on various signaling pathways regulating cell survival such as Akt, mitochondrial activity, and apoptosis. Although commonly thought of as a toxic gas, low concentrations of hydrogen sulfide have been shown to be beneficial in promoting tissue survival post-ischemia, and modulate a wide variety of cellular responses. This review will detail the mechanisms of hydrogen sulfide in affecting the Akt signaling pathway, mitochondrial function, and apoptosis, particularly in regards to ischemic reperfusion injury in muscle tissue. It will conclude with potential clinical applications of hydrogen sulfide, combinations with other therapies, and perspectives for future studies.

Cystathionine gamma‐lyase/H 2 S signaling facilitates myogenesis under aging and injury condition

“…More directly, exogenous administration of H 2 S increased muscle mass and cross‐sectional area in both WT and CSE‐KO mice post‐CTX‐injection. Consistent with our findings, several lines of evidence validated that H 2 S induced muscle development in chicks and also mice 20,45,49 . Taken together, these results identify the CSE/H 2 S system as an important regulator of muscle regeneration.…”

“…H 2 S protects diaphragm muscle fibrosis and strengthens diaphragmatic biomechanical properties in streptozotocin‐induced diabetic rats 44 . H 2 S also alleviates the injury of skeletal muscle in ischemia‐reperfusion rats, improves muscle functions in high‐fat‐diet‐fed mice, and increases muscle mass in db/db diabetic mice 20,43,45,46 . We and others recently discovered that H 2 S suppresses angiotensin II or hyperhomocysteinemia‐induced skeletal muscle atrophy in mice via mitigation of endoplasmic reticulum stress and Golgi's stress response 47,48 .…”

Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys

“…H 2 S can induce this hypometabolism through reversible inhibition of mitochondrial electron transport chain (ETC), more specifically complex IV (cytochrome c oxidase)[11,12]. Next to inhibition, H 2 S protects the ETC by different mechanisms[13]. Indeed, gaseous administration of H 2 S in mice induces a hypometabolic state of suspended animation[12], prevents renal injury in mice during IRI[14] and is promising in decreasing ROS damage[15–16].…”

Freeze-Dried Extracellular Vesicles From Adipose-Derived Stem Cells Prevent Hypoxia-Induced Muscle Cell Injury

“…For the control group, the ischemic myoblasts were treated with freshly prepared EVs (50 µg/µL) in 1X PBS. We also ran parallel experiments where ischemic myoblasts were treated either with phenol red-free DMEM supplemented with 1% FBS as a control group or with different concentrations of sodium hydrosulfide NaHS or sodium hydrosulfide donor (GYY4137, Cayman Chemical), since hydrogen sulfide has previously been shown to attenuate ischemic injury (Henderson et al, 2011;Wetzel and Wenke, 2019) we were interested in comparing the efficiency of exosomes treatment to other treatment approaches.…”