Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells.
Cellular stress may stimulate cell survival pathways or cell death depending on its severity. 6-Hydroxydopamine (6-OHDA) is a neurotoxin that targets dopaminergic neurons that is often used to induce neuronal cell death in models of Parkinson's disease. Here we present evidence that 6-OHDA induces apoptosis in rat PC12 cells that involves release of cytochrome c and Smac/Diablo from mitochondria, caspase-3 activation, cleavage of PARP, and nuclear condensation. 6-OHDA also induced the heat shock response, leading to increased levels of Hsp25 and Hsp70. Increased Hsp25 expression was associated with cell survival. Prior heat shock or overexpression of Hsp27 (human homologue of Hsp25) delayed cytochrome c release, caspase activation, and reduced the level of apoptosis caused by 6-OHDA. We conclude that 6-OHDA induces a variety of responses in cultured PC12 cells ranging from cell survival to apoptosis, and that induction of stress proteins such as Hsp25 may protect cells from undergoing 6-OHDA-induced apoptosis.
Gorman
Adrienne M
AM
Department of Biochemistry and the National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Szegezdi
Eva
E
Quigney
Declan J
DJ
Samali
Afshin
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D015938:Complement Membrane Attack Complex; C489013:DIABLO protein, rat; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D009498:Neurotoxins; C047610:SC5b-9 protein complex; D016627:Oxidopamine; D003165:Complement System Proteins; D045304:Cytochromes c; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases