Effect of hydrogen sulfide on glycolysis‐based energy production in mouse erythrocytes

• Published in: Journal of cellular physiology Vol. 237; no. 1; pp. 763 - 773
• Main Authors: Wondimu, Eden T., Zhang, Quanxi, Jin, Zhuping, Fu, Ming, Torregrossa, Roberta, Whiteman, Matthew, Yang, Guangdong, Wu, Lingyun, Wang, Rui
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2022
• Subjects: 3‐mercaptopyruvate sulfur transferase; Adenosine Triphosphate - metabolism; Anaerobic processes; Animals; ATP; ATP production; Cell viability; Energy; Erythrocytes; Erythrocytes - metabolism; Erythropoiesis; Glucose metabolism; Glycolysis; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - pharmacology; Hypoxia; Incubation; Low concentrations; Mammalian cells; Mammals; Mammals - metabolism; Mice; Mitochondria; Oxygenation; red blood cell; Substrate inhibition; Sulfurtransferase; hypoxia; ATP production; 3-mercaptopyruvate sulfur transferase; glycolysis; red blood cell
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30544

Hydrogen sulfide (H2S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2S on glycolysis‐mediated energy production. The purpose of this study was to determine the effect of H2S on glycolysis‐mediated energy production in mitochondria‐free mouse RBCs. Western blot analysis showed that the only H2S‐generating enzyme expressed in mouse RBCs is 3‐mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2S. Both exogenously administered H2S salt and MST‐derived endogenous H2S stimulated glycolysis‐mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2S levels and MST activity in mouse RBCs. The mitochondria‐targeted H2S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3–100 μM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300–1000 μM) lowered ATP levels, but prolonged cell viability. H2S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen‐independent energy production. The effect of H2S on glycolysis‐mediated energy production has not been studied in depth. Here, we report that mouse red blood cells (RBCs), which rely solely on glycolysis for energy production, have the capacity to endogenously produce H2S and that H2S stimulates glycolysis. Moreover, exposure of RBCs to H2S salt significantly prolonged the lifespan of mouse RBCs ex vivo, indicating that H2S may have a functional impact on RBC survival.