Exogenous Hydrogen Sulfide Plays an Important Role Through Regulating Autophagy in Ischemia/Reperfusion Injury

Abstract

Ischemia/reperfusion (I/R) injury is characterized by limiting blood supply to organs, then restoring blood flow and reoxygenation. It leads to many diseases, including acute kidney injury, myocardial infarction, circulatory arrest, ischemic stroke, trauma, and sickle cell disease. Autophagy is an important and conserved cellular pathway, in which cells transfer the cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. Hydrogen sulfide (H₂S), along with carbon monoxide (CO) and nitric oxide (NO), is an important gas signal molecule and regulates various physiological and pathological processes. In recent years, there are many studies on the improvement of I/R injury by H₂S through regulating autophagy, but the related mechanisms are not completely clear. Therefore, we summarize the related research in the above aspects to provide theoretical reference for future in-depth research.

Keywords: apoptosis; autophagy; hydrogen sulfide; ischemia/reperfusion injury; oxidative stress.

FIGURE 1

Schematic diagram of the mechanism of ischemia/reperfusion (I/R) injury. Ischemia increases intracellular and mitochondrial calcium levels by interfering with ATPase dependent ion transport. At the same time, the mechanism of cell volume regulation is also destroyed by the lack of ATP, which can cause the dissolution of organelles and plasma membranes. Although reperfusion can save hypoxic tissue, it can promote the production of reactive oxygen species, isolate pro-inflammatory immune cells in ischemic tissue, and aggravate tissue injury.