Induction of Hsp68 by oxidative stress involves the lipoxygenase pathway in C6 rat glioma cells.
The induction of Hsp68 by heat shock (HS) and oxidative stress (OS) involves different pathways in C6 rat glioma cells. The pathways were analyzed by specific inhibitors of signal transduction cascades. Quercetin (inhibitor of PLA(2) and lipoxygenase) inhibited only the OS-induced but not the HS-induced expression of Hsp68. Preincubation with quinacrine (inhibitor of PLA(2)) before stress also suppressed the expression of Hsp68 only after oxidative stress. Moreover, another inhibitor of lipoxygenase (alpha-tocopherol) exclusively suppressed OS-induced Hsp68 expression. This different regulation was confirmed by exposing the cells to arachidonic acid (AA) during stress which strongly increased the induction of Hsp68 only after OS. PGE(2) (metabolite of cyclooxygenase) and indomethacin (inhibitor of cyclooxygenase) had no influence on Hsp68 expression in response to both stressors. The results suggest that the induction of Hsp68 by oxidative stress is mainly transmitted by the lipoxygenase pathway in C6 rat glioma cells.
Gosslau
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Institute of Cell Biology, Biochemistry and Biotechnology, University of Bremen, P.O. Box 330440, D-28334, Bremen, Germany.
Rensing
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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; C097210:Hspa1a protein, rat; D016718:Arachidonic Acid; D008084:Lipoxygenase