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Heat shock and ceramide have different apoptotic pathways in radiation induced fibrosarcoma (RIF) cells

Title
Heat shock and ceramide have different apoptotic pathways in radiation induced fibrosarcoma (RIF) cells
Authors
Kim H.-J.Lee K.-J.
Ewha Authors
이공주김희정
SCOPUS Author ID
이공주scopus; 김희정scopusscopusscopus
Issue Date
2002
Journal Title
Molecular and Cellular Biochemistry
ISSN
0300-8177JCR Link
Citation
vol. 229, no. 1-2, pp. 139 - 151
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Heat shock induces various cellular responses including inhibition of protein synthesis, production of heat shock proteins (HSPs) and induction of thermotolerance. The molecular mechanisms of the processes have not been well understood. It has been proposed that ceramide formation during heat shock mediates heat shock induced apoptosis. We examined whether C2-ceramide mimicked the cellular response to heat shock in RIF-1 cells and their thermotolerant derivative TR-RIF-1 cells. Discernible effects between heat shock and C2-ceramide treatments were observed in cellular changes such as total protein synthesis, HSP synthesis, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activity and PARP cleavage. Heat shock immediately inhibited cellular protein synthesis, which was recovered by synthesizing HSPs first and then whole proteins later. Heat shock also activated SAPK/JNK and increased PARP cleavage in dose-dependent manner. Thermotolerant TR-RIF-1 cells responded to heat shock more insensitively than RIF-1 cells. On the other hand, C2-ceramide treatment did not accompany any changes induced by heat shock. No discernible differences between RIF-1 and TR-RIF-1 cells were observed by C2-ceramide treatment. We tried to figure out how C2-ceramide interacts with cellular membrane and found that exogenous C2-ceramide was incorporated into the outer monolayer and flipped into the inner monolayer of human erythrocytes in ATP-dependent manner. However, the rate of C2-ceramide incorporation was similar in control and thermotolerant cells. In summary, thermotolerant cells are resistant to heat shock induced apoptotic signaling but not resistant, rather sensitive to membrane disturbing C2-ceramide mediated apoptosis. These results suggest that heat shock and ceramide have different signal transduction pathways.
DOI
10.1023/A:1017941131744
Appears in Collections:
약학대학 > 약학과 > Journal papers
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