Document Detail


p38 MAPK activation and mitochondrial depolarization mediate the cytotoxicity of Taiwan cobra phospholipase A2 on human neuroblastoma SK-N-SH cells.
MedLine Citation:
PMID:  18582542     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Modification of catalytic residue His-47 with p-bromophenacyl bromide (BPB) abolished the enzymatic activity of Naja naja atra phospholipase A2 (PLA2). Additionally, alterations in the global structure and the spatial positions of Trp residues were noted in His-modified PLA2. The cell viability of human neuroblastoma SK-N-SH cells was decreased by approximately 40% and 20% after treatment with 10 microM PLA2 and BPB-PLA2, respectively. Native and His-modified PLA2 induced a necrotic cell death accompanied with an activation of p38 MAPK, the loss of mitochondrial membrane potential (DeltaPsim) and cytochrome c release. Pretreatment with SB202190 (p38 MAPK inhibitor) and cyclosporine A (inhibitor of mitochondria permeability transition pore) rescued cell viability, DeltaPsim and cytochrome c release of PLA2-treated cells. Taken together, our data indicate that PLA2 activity does not play an indispensable role on the cytotoxicity of N. naja atra PLA2, and suggest a novel function of secretory PLA2 in inducing cell death of neuroblastoma. Moreover, the reduced cytotoxicity noted with BPB-PLA2 may be partly attributed to conformational distortion after modification of His-47.
Authors:
Ku-Chung Chen; Pei-Hsiu Kao; Shinne-Ren Lin; Long-Sen Chang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  Toxicology letters     Volume:  180     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-09-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  53-8     Citation Subset:  IM    
Affiliation:
Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cell Survival / drug effects
Cobra*
Cobra Venoms / chemistry,  toxicity*
Cytochromes c / metabolism
Enzyme Inhibitors / pharmacology
Humans
Imidazoles / pharmacology
Membrane Potential, Mitochondrial / drug effects*
Necrosis / chemically induced
Neuroblastoma / drug therapy,  metabolism,  pathology
Phospholipases A2 / antagonists & inhibitors,  chemistry,  toxicity*
Pyridines / pharmacology
p38 Mitogen-Activated Protein Kinases / biosynthesis*
Chemical
Reg. No./Substance:
0/4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; 0/Cobra Venoms; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Pyridines; 9007-43-6/Cytochromes c; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.1.4/Phospholipases A2

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


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