Involvement of the acid sphingomyelinase pathway in UVA-induced apoptosis

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Zhang YG, Mattjus P, Schmid PC, Dong ZM, Zhong SP, Ma WY, Brown RE, Bode AM, Schmid HHO, Dong ZG
Publication year: 2001
Journal: Journal of Biological Chemistry
Journal acronym: J BIOL CHEM
Volume number: 276
Issue number: 15
Start page: 11775
End page: 11782
Number of pages: 8
ISSN: 0021-9258
eISSN: 1083-351X


Abstract

The sphingomyelin-ceramide pathway is an evolutionarily conserved ubiquitous signal transduction system that regulates many cell functions including apoptosis. Sphingomyelin (SM) is hydrolyzed to ceramide by different sphingomyelinases. Ceramide serves as a second messenger in mediating cellular effects of cytokines and stress. In this study, we find that acid sphingomyelinase (SMase) activity was induced by UVA in normal JY lymphoblasts but was not detectable in MS1418 lymphoblasts from Niemann-Pick type D patients who have an inherited deficiency of acid SMase. We also provide evidence that WA can induce apoptosis by activating acid SMase in normal JY cells. In contrast, UVA-induced apoptosis was inhibited in MS1418 cells. Exogenous SMase and its product, ceramide (10-40 muM), induced apoptosis in JY and MS1418 cells, but the substrate of SMase, SM (20-80 muM), induced apoptosis only in JY cells. These results suggest that UVA-induced apoptosis by SM is dependent on acid SMase activity. We also provide evidence that induction of apoptosis by WA may occur through activation of JNKs via the acid SMase pathway.

Last updated on 2019-14-12 at 02:59