Pro- and anti-apoptotic effects of K+ in HeLa cells.
The present study determined the effects of osmotic stress induced by sorbitol and KCl on apoptosis. Sorbitol induced apoptosis, activated the mitogen-activated protein kinase (MAPK) family and stimulated accumulation of cytosolic cytochrome c and procaspase-3 cleavage. KCl (0.2 M) also activated the MAPKs and induced cytosolic cytochrome c accumulation but did not induce procaspase-3 cleavage or apoptosis and was protective against sorbitol-induced apoptosis. However, when cells were exposed to KCl for 1 h, washed and returned to isotonic medium, caspase-3 was rapidly cleaved and apoptosis induced. We conclude that hyperosmotic KCl initiates early events in apoptosis but blocks caspase-3 activation by preventing the loss of intracellular K+.
Bilney
A J
AJ
School of Biological Sciences, Flinders University of South Australia, Adelaide.
Murray
A W
AW
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009995:Osmosis / Q000187:drug effects; D009997:Osmotic Pressure; D011188:Potassium / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D003574:Cytochrome c Group; D013012:Sorbitol; D011189:Potassium Chloride; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D011188:Potassium