HSP60, Bax, and cardiac apoptosis.
HSP60 has long been known as an important chaperonin and as having key folding functions within the mitochondria. However, it has now become evident that significant amounts of HSP60 are found in extra-mitochondrial locations. This extra-mitochondrial HSP60 in the heart has key anti-apoptotic functions. Extra-mitochondrial HSP60 complexes with both bax and bak, but not with bcl-2. Reduction in HSP60 is sufficient to precipitate apoptosis. In the setting of hypoxia and reoxygenation HSP60 decreases with reoxygenation, but the apoptotic cascade has already been triggered by end-hypoxia. Redistribution of cytosolic HSP60 to the plasma membrane during hypoxia appears to contribute to the initiation of the apoptotic cascade with hypoxia and reoxygenation.
Knowlton
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AA
Cardiovascular Division, Department of Medicine, University of California, Davis 95616, USA. aaknowlton@ucdavis.edu
Gupta
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S
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018834:Chaperonin 60 / Q000235:genetics*; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D016376:Oligonucleotides, Antisense; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D018834:Chaperonin 60; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein