연구성과

Hydrogen sulfide (H2S) functions as a physiological gastransmitter in both normal and pathophysiological cellularevents. H2S is produced from substances by three enzymes:cystathionine b-synthase (CBS), cystathionine c-lyase (CSE),and 3-mercaptopyruvate sulfurtransferase (MST). In humantissues, these enzymes are involved in tissue-specific biochemicalpathways for H2S production. For example, CBS andcysteine aminotransferase/MST are present in the brain, butCSE is not. Thus, we examined the expression of H2Sproduction-related enzymes in peripheral nerves. Here, wefound that CSE and MST/cysteine aminotransferase, but notCBS, were present in normal peripheral nerves. In addition,injured sciatic nerves in vivo up-regulated CSE in Schwanncells during Wallerian degeneration (WD); however, CSE wasnot up-regulated in peripheral axons. Using an ex vivo sciaticnerve explant culture, we found that the inhibition of H2Sproduction broadly prevented the process of nerve degeneration,including myelin fragmentation, axonal degradation,Schwann cell dedifferentiation, and Schwann cell proliferationin vitro and in vivo. Thus, these results indicate that H2Ssignaling is essential for Schwann cell responses to peripheralnerve injury. Keywords: axonal degradation, cytstathionine-c-lyase (CSE),demyelination, hydrogen sulfide, Schwann cells, Wallerian degeneration