Hsp70 suppresses apoptosis in sympathetic neurones by preventing the activation of c-Jun.
The anti-apoptotic effects of heat-shock protein (Hsp70) were assessed in SCG neurones following nerve growth factor (NGF) withdrawal. The results showed that the virally mediated expression of Hsp70 mirrored the effects of the c-Jun-N-terminal kinase (JNK) binding domain (JBD) of JNK interacting protein (an inhibitor of JNK and c-Jun activation) and suppressed the phosphorylation of c-Jun. Preventing c-Jun transcriptional activity subsequently led to reduced cytochrome c release and prevented caspase activation as indicated by a decrease in poly (ADP-ribose) polymerase-1 (PARP) cleavage. Together, these results show that Hsp70 is a highly effective inhibitor of apoptosis in sympathetic neurones and that it mediates this effect primarily by suppressing c-Jun transcriptional signalling.
Bienemann
A S
AS
Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
Lee
Y B
YB
Howarth
J
J
Uney
J B
JB
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000166:cytology*; D014162:Transfection / Q000379:methods
D018840:HSP70 Heat-Shock Proteins; D016755:Proto-Oncogene Proteins c-jun; D049452:Green Fluorescent Proteins; D045304:Cytochromes c; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; C058796:ADP-ribose pyrophosphatase I; D011755:Pyrophosphatases