Document Detail


PACAP prevents toxicity induced by cisplatin in rat and primate neurons but not in proliferating ovary cells: involvement of the mitochondrial apoptotic pathway.
MedLine Citation:
PMID:  18652895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cisplatin is a chemotherapeutic agent whose use is limited by side effects including neuropathies. In proliferating cells, toxic action of cisplatin is based on DNA interactions, while, in quiescent cells, it can induce apoptosis by interacting with proteins. In the present study, we compared cytotoxic mechanisms activated by cisplatin in primate and rodent neurons and in ovary cells in order to determine whether the anti-apoptotic peptide PACAP could selectively reduce neurotoxicity. In quiescent neurons, JNK and sphingomyelinase inhibitors blocked cisplatin-induced cell death. Toxicity was associated with DNA laddering, caspase-3 and -9 activations and Bax induction. These effects were prevented by PACAP. In proliferating cells, cisplatin activated caspase-8 but had no effect on caspase-9. PACAP exerted no protective effect. These data indicate that cisplatin activates distinct apoptotic pathways in quiescent neurons and proliferating cells and that PACAP may reduce neurotoxicity of cisplatin without affecting its chemotherapeutic efficacy.
Authors:
Nicolas Aubert; David Vaudry; Anthony Falluel-Morel; Arnaud Desfeux; Cécile Fisch; Philippe Ancian; Stéphane de Jouffrey; Jean-François Le Bigot; Alain Couvineau; Marc Laburthe; Alain Fournier; Vincent Laudenbach; Hubert Vaudry; Bruno J Gonzalez
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-03
Journal Detail:
Title:  Neurobiology of disease     Volume:  32     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-16     Completed Date:  2009-05-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-80     Citation Subset:  IM    
Affiliation:
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology*
Apoptosis Regulatory Proteins / physiology*
CHO Cells
Callithrix
Cell Proliferation / drug effects
Cells, Cultured
Cisplatin / antagonists & inhibitors*,  therapeutic use,  toxicity
Cricetinae
Cricetulus
Female
Macaca fascicularis
Male
Mitochondrial Proteins / physiology*
Neurons / cytology,  drug effects,  physiology*
Organ Culture Techniques
Ovary / cytology*,  drug effects,  physiology*
Pituitary Adenylate Cyclase-Activating Polypeptide / physiology*
Rats
Rats, Wistar
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Mitochondrial Proteins; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 15663-27-1/Cisplatin

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