Item – Theses Canada

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OCLC number
46585173
Author
Baker, Alison Dawn,1972-
Title
Role of ceramide in induction of Fos, Jun, and collagenase in chondrocytes.
Degree
M. Sc. -- University of Toronto, 1997
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [1999]
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
Arthritis is marked by increased expression of collagenase, which is induced by IL-1. IL-1 is found at increased levels in arthritic joints, and stimulates mRNA expression of c-fos and c-jun, whose products comprise AP-1, a transcription factor necessary for IL-1-induced collagenase expression. Previous data also implicate IL-1 in sphingomyelin hydrolysis to the second messenger ceramide. IL-1 induced ceramide release in chondrocytes, and ceramide activated c-fos, and c-jun, but not collagenase expression. The induction of c-fos was specific, transient, and transcriptionally and post-transcriptionally regulated. Ceramide potentiated the effect of low IL-1 concentrations, indicating that ceramide is not solely a second messenger. Ceramide induction of c-fos was not accompanied by increased SRE binding, nor did it involve MAPK activation, or ROS as signalling intermediates, but did involve increased SRE transcriptional activity. Ceramide did not induce collagenase expression, but did increase AP-1 transcriptional activity. At high concentrations of ceramide, MMP induction was inhibited. Thus, ceramide appears to function separately from IL-1 through a MAPK-independent pathway that is sufficient to induce c-fos expression.
ISBN
0612293084
9780612293083