Hydrogen sulfide (H2S) functions as a signaling molecule and cytoprotectant. In many tissues, H2S is produced from l-cysteine, whereas the kidney also produces H2S from d-cysteine by the sequential activities of d-amino acid oxidase (DAO) and 3-mercaptopyruvate sulfurtransferase (3MST). The d-cysteine pathway produces H2S more efficiently than the l-cysteine pathway, and d-cysteine significantly reduces ischemia-reperfusion injury in the renal cortex compared with l-cysteine. However, the specific renal cell types responsible for the d-cysteine pathway have not been clearly identified. Here, we show that a subpopulation of MDCK (NBL-2) cells, a renal epithelial cell line, expresses both DAO and 3MST. MDCK cells initially produced H2S from d-cysteine, but this activity progressively declined with passage. In contrast, clonal cells expressing DAO and 3MST, established from this subpopulation, maintained stable H2S production. The clonal cells exhibited two distinct patterns of DAO expression: one showed increased DAO levels after confluence, whereas the other displayed high DAO expression even before reaching confluence. These findings suggest that the d-cysteine pathway operates in epithelial cells and plays distinct roles depending on cellular state and dynamics. Moreover, the established clonal cells may provide insight into the role of d-cysteine-mediated H2S production in the kidney.
Miyamoto et al. (Tue,) studied this question.
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