Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis / physiology*
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Cell Survival
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Cells, Cultured
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Cytochromes c / metabolism
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Enzyme Activation
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Green Fluorescent Proteins / metabolism
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HSP70 Heat-Shock Proteins / metabolism*
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mitochondria / metabolism
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Nerve Growth Factor / metabolism
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Neurons / physiology*
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Proto-Oncogene Proteins c-jun / metabolism*
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Pyrophosphatases / metabolism
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Rats
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Rats, Wistar
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Signal Transduction / physiology
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Superior Cervical Ganglion / cytology*
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Transfection / methods
Substances
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HSP70 Heat-Shock Proteins
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Proto-Oncogene Proteins c-jun
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Green Fluorescent Proteins
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Cytochromes c
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Nerve Growth Factor
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JNK Mitogen-Activated Protein Kinases
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ADP-ribose pyrophosphatase I
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Pyrophosphatases