Document Detail


p44/42 MAP kinase and c-Jun N-terminal kinase contribute to the up-regulation of caspase-3 in manganese-induced apoptosis in PC12 cells.
MedLine Citation:
PMID:  16787641     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caspase-3 (32 kDa) is one of the primary protease executioners of apoptosis and is activated by intra-chain proteolytic cleavage, which generates a large subunit (17 kDa) and a small subunit (12 kDa). Typically, after apoptotic stimuli, the level of cleaved caspase-3 increases while that of caspase-3 decreases. It has been shown that caspase-3 mRNA levels increase in cortex following traumatic brain injury or focal ischemia. In the present study, we demonstrate that both caspase-3 mRNA and protein increase in apoptotic PC12 cells following exposure to manganese which strongly induces caspase-3 cleavage. Up-regulation of caspase-3 protein was evident in manganese-treated PC12 cells and was moderate in cisplatin-, rotenone- and A23187-treated cells but was not observed in serum deprivation-, anisomycin-, camptothecin-, cycloheximide- or staurosporine-treated cells in which all treatments induced extensive DNA fragmentation. Manganese-induced up-regulation of caspase-3 mRNA was partially attenuated by the pretreatment with the MEK inhibitor U0126, but not with the c-Jun N-terminal kinase (JNK) inhibitor SP600125. In contrast, the increase in caspase-3 protein was suppressed by both U0126 and SP600125. These results suggest that p44/42 MAPK contributes to the up-regulation of caspase-3 mRNA and the JNK pathway regulates caspase-3 protein levels posttranslationally in manganese-induced apoptosis in PC12 cells.
Authors:
Yoshimasa Ito; Kentaro Oh-Hashi; Kazutoshi Kiuchi; Yoko Hirata
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-19
Journal Detail:
Title:  Brain research     Volume:  1099     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-25     Completed Date:  2006-09-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Affiliation:
Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Blotting, Western / methods
Caspase 3
Caspases / genetics,  metabolism*
Drug Interactions
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
JNK Mitogen-Activated Protein Kinases / physiology*
Manganese / pharmacology*
Mitogen-Activated Protein Kinase 1 / physiology*
PC12 Cells
RNA, Messenger / biosynthesis
Rats
Reverse Transcriptase Polymerase Chain Reaction / methods
Signal Transduction / drug effects,  physiology
Time Factors
Up-Regulation / drug effects*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/RNA, Messenger; 7439-96-5/Manganese; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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