engleski

Role of stress proteins in development of apoptosis

Apoptosis is molecularly programmed cell death that can be induced by environmental, physical or chemical stresses. Its triggering involves activation of stress– kinases including JNK and p38. Cellular resistance to stress is mediated by the expression of heat shock proteins (HSPs). The HSP70 family is involved in maintaining cellular survival and includes both constitutive and inducible members. The survival promoting effects of HSPs can be partly attributed to the suppression of apoptosis. OBJECTIVE of this paper was to present evidence for functional interactions between HSP70 and elements of apoptotic machinery and to suggest how they might affect cellular susceptibility to damaging stimuli. We used Western blot analysis to determine expression of HSP70 in rat kidneys and expression of HSP70 and activation of ERK, JNK and p38 in LLC-PK1 cells treated with low doses of ochratoxin A (OTA), a well-known nephrotoxic and genotoxic mycotoxin. RESULTS showed that control animals produced 68- and 74-kDa HSP70 isoforms in the relative proportion 81:19 %, which changed to 10: 90% after 10 days of treatment, than was normalised after 30 days and changed again after 60 days, indicating only a short-term normalisation. OTA treatment did not change the total amount of HSP70 expressed in rat kidney. No changes in the HSP70 levels were detected in the cells treated with OTA, although cells were seriously injured, as seen from the reduced viability and increased release of LDH. Cells showed normal HSP70 induction following a heat shock. Exposure to OTA before the heat shock prevented HSP70 induction. We observed short and transient activation of ERK and intense activation of JNK and p38 following 12 and 48 hours of treatment. Results indicate that OTA does not induce HSP70 in rat kidney or in cultured cells. The absence of HSP70 protective effects might be a possible explanation for the cumulative destructive effects of OTA and a silent onset of endemic nephropathy in humans.

stress proteins; apoptosis

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