Involvement of the acid sphingomyelinase pathway in UVA-induced apoptosis

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Zhang YG, Mattjus P, Schmid PC, Dong ZM, Zhong SP, Ma WY, Brown RE, Bode AM, Schmid HHO, Dong ZG
Publiceringsår: 2001
Tidskrift: Journal of Biological Chemistry
Tidskriftsakronym: J BIOL CHEM
Volym: 276
Nummer: 15
Artikelns första sida, sidnummer: 11775
Artikelns sista sida, sidnummer: 11782
Antal sidor: 8
ISSN: 0021-9258
eISSN: 1083-351X


Abstrakt

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.

Senast uppdaterad 2019-10-12 vid 03:33