Pivotal role of reactive oxygen species as intracellular mediators of hyperthermia-induced apoptosis

Abstract

The effects of cellular antioxidant capacity on hyperthermia (HT)- induced apoptosis and production of anti-apoptotic heat shock proteins (HSPs) were investigated in HL-60 cells and in HL-60AR cells that are characterized by an elevated endogenous catalase activity. Exposure of both cell lines to 43 °C for 1 h in]flared apoptosis. Apoptasis peaked at 3-6 h after heat exposure in the HL-60 cells. Whereas HL-60AR cells were partially protected against HT-induced apoptosis at these early time points, maximal levels of apoptosis were detected later, i.e. 12-18 h after heat exposure. This differential induction of apoptosis was directly corn-elated to the induction of the antiapoptotic HSP27 and HSP70. In particular, in the HL-69 cells HSP27 was significantly induced at 12-18 h after exposure to 43 °C when apoptosis dropped. In contrast, coinciding with the late onset of apoptasis in HL-60AR cells at that time HL-60AR cells lacked a similar HSP response. In line with the higher antioxidant capacity HL-60AR cells accumulated reactive oxygen species to a lesser degree than HL-6O cells after heat treatment. Protection from HT-induced apoptosis as well as diminished heat-induced HSP27 expression was also observed after cotreatment of HL-60 cells with 43 °C and catalase but not with superoxide dismutase. These data emphasize the pivotal role of reactive oxygen species for HT induced pro- and antiapoptotic pathways.