Pivotal role of reactive oxygen species as intracellular mediators of hyperthermia-induced apoptosis.
The effects of cellular antioxidant capacity on hyperthermia (HT)-induced apoptosis and production of antiapoptotic 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 degrees C for 1 h initiated apoptosis. Apoptosis 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 correlated to the induction of the antiapoptotic HSP27 and HSP70. In particular, in the HL-60 cells HSP27 was significantly induced at 12-18 h after exposure to 43 degrees C when apoptosis dropped. In contrast, coinciding with the late onset of apoptosis 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-60 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 degrees 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.
Katschinski
D M
DM
Institute of Physiology, Medical University of Lübeck, D-23538 Lübeck, Germany. katschinski@physio.mu-luebeck.de
Boos
K
K
Schindler
S G
SG
Fandrey
J
J
D017209:Apoptosis / Q000502:physiology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D018922:HL-60 Cells; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D007700:Kinetics; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics*; D009842:Oligopeptides / Q000378:metabolism; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000502:physiology*; D014158:Transcription, Genetic; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D003374:Coumarins; D005456:Fluorescent Dyes; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; D051020:bcl-X Protein; D002374:Catalase