Role of MAPKs in heat-induced apoptosis

초록

External insults including DNA-damaging chemotherapeutic drugs, ultraviolet irradiation, and heat shock stimulate a recently identified cytoplasmic signaling system that is structurally related to the mitogen activated protein kinase (MAPK) pathway. The three principal MAPK signaling cascades are denoted the ERK 1/2 for cell survival, JNK/SAPK and p38 MAPK pathways for cell death. It has been known that an exposure of HL60 human promyelocytic leukaemia cells to acidic media with pH 6.6-6.0 caused an apoptosis and that an acidic environment enhances hyperthermic cell killing. However it is unclear whether the activation of the MAP kinases and heat-induced apoptosis in HL60 cells are related. In the present report, to study signaling pathway underlying acidic-, or hyperthermia-induced apoptosis in HL60 cells, the activation of MAPKs after various environmental pHs ranging from 7.5 to 6.0 or heat treatment (43℃, 1 hour) was examined by immunocomplex kinase assay, western blot analysis and induction of apoptosis by these stresses was investigated through the DNA fragmentation by agarose gel electrophoresis, flow cytometric analysis of DNA content. The activation of MAPKs in human promyelocytic leukemia HL60 cell lines could not be visible to acid-induced death suggesting that other pathways are contributing to apoptosis physiologically.