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Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase.

Authors
Huang-C; Ma-WY; Ding-M; Bowden-GT; Dong-Z
Source
J Biol Chem 1997 Oct; 272(44):27753-27757
NIOSHTIC No.
20033923
Abstract
Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in UV-induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 ~3% residual acid SMase activity) lymphoblast cell line, MS1418. The results showed that while UV irradiation markedly induces JNK activation in a normal human lymphoblast cell line, JY, it induces only weak JNK activation in MS1418 cells. This difference of JNK response to UV irradiation between these two cell lines was further observed in time course and dose-response studies. In contrast, 12-O-tetradecanoylphorbol-13-acetate-induced JNK activation could be observed in both JY and MS1418 cells. Furthermore, significant JNK activation can be observed in MS1418 cells by exposure of the cells to SMase or C2-ceramide, whereas phospholipase A2 or phospholipase C did not show significant induction of JNK activity, and C2-dihydroceramide and sphingosine induce only much weaker JNK activation in MS1418 cells than that by C2-ceramide. These data demonstrated that SMase plays an essential role in UV-induced JNK activation.
Keywords
Ultraviolet-radiation; Radiation-effects; Radiation-properties; Cell-growth; Cellular-reactions; Genetic-factors; Irradiation
Contact
Z. Dong, The Hormel Institute, University of Minnesota, 801 16th Ave. NE, Austin, MN 55912
CODEN
JBCHA3
Publication Date
19971001
Document Type
Journal Article
Email Address
zgdong@wolf.co.net
Fiscal Year
1998
NTIS Accession No.
NTIS Price
Issue of Publication
44
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
MN; WV; AZ
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