Induction of cystathionine gamma-lyase expression and metallothionein-1 S-sulfhydration alleviate cadmium-induced cell death in myoblast cells

Abstract Hydrogen sulfide (H 2 S), a multifunctional gasotransmitter, participates in a wide range of cellular signal transduction and pathophysiological processes. Cystathionine gamma-lyase (CSE) acts as a major H 2 S-generating enzyme in peripheral organs and tissues. As a cysteine-rich and heavy metal-binding protein, metallothionein-1 (MT-1) is known to protect cells from various environmental stresses. Here we demonstrated that exposure of cadmium (Cd) induced oxidative stress, depleted intracellular thiols, and stimulated apoptotic cell death in mouse myoblast cells. CSE expression and H 2 S production were significantly enhanced by Cd treatment. NaHS, a well-known H 2 S donor, at physiologically relevant concentration significantly alleviated Cd-induced damage in both myoblasts and mouse skeletal muscles. In contrast, down-regulation of CSE/H 2 S system deteriorated Cd-stimulated oxidative stress and cell death. Exposure of the cells to Cd lead to increased expressions of metal regulatory transcription factor 1 and MT-1, while siRNA-mediated MT-1 knockdown alleviated Cd-induced CSE expression and caused more oxidative stress and cell death. In addition, H 2 S post-translationally modified MT-1 by S -sulfhydration and stabilized zinc-protein complex. Taken together, these data suggest that CSE/H 2 S system would protect myoblasts and skeletal muscles from Cd-induced damage by S -sufhydrating MT-1.