Document Detail


Reversible activation of secretory phospholipase A2 by sulfhydryl reagents.
MedLine Citation:
PMID:  15752719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Secretory phospholipase A(2)s (sPLA(2)s) have been implicated in physiological and pathological events, but the regulatory mechanism(s) of their activities in cells remains to be solved. Previously, we reported that phenylarsine oxide (PAO), a sulfhydryl reagent, stimulated arachidonic acid (AA) release in rat pheochromocytoma PC12 cells. In this study, we examined the effects of thimerosal, another sulfhydryl reagent, to clarify the sulfhydryl modification and activation of sPLA(2) molecules in cells. Like PAO, thimerosal-stimulated AA release in an irreversible manner and the responses were not additive. Dithiol compounds such as dithiothreitol inhibited AA release from both the thimerosal- and the PAO-treated cells, and monothiol compounds (l-Cys and glutathione) decreased the thimerosal response. Both sulfhydryl reagents stimulated AA release from the HEK293T cells expressing human sPLA(2)X, and stimulated the sPLA(2) activities of bee venom sPLA(2) and the soluble fraction of sPLA(2)X-expressing cells. Our results suggest that the sPLA(2)s in cells are inactive and modification of disulfide bonds in the molecules can be a trigger of sPLA(2) activation in cells. Sulfhydryl reagents are useful tools for studying the regulatory mechanism(s) of sPLA(2) activity in cells.
Authors:
Maiko Nabemoto; Keiko Ohsawa; Hiroyuki Nakamura; Tetsuya Hirabayashi; Takeshi Saito; Yasunobu Okuma; Yasuyuki Nomura; Toshihiko Murayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  436     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-08     Completed Date:  2005-05-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  145-53     Citation Subset:  IM    
Affiliation:
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenicals / pharmacology
Calcium / metabolism
Cysteine / pharmacology
Dithiothreitol / pharmacology
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology*
Glutathione / pharmacology
Group II Phospholipases A2
Humans
PC12 Cells
Phospholipases A / drug effects,  metabolism*
Phospholipases A2
Rats
Receptors, Cell Surface / metabolism
Sulfhydryl Reagents / pharmacology*
Thimerosal / pharmacology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Arsenicals; 0/Enzyme Inhibitors; 0/Receptors, Cell Surface; 0/Sulfhydryl Reagents; 3483-12-3/Dithiothreitol; 52-90-4/Cysteine; 54-64-8/Thimerosal; 637-03-6/oxophenylarsine; 70-18-8/Glutathione; 7440-70-2/Calcium; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Group II Phospholipases A2; EC 3.1.1.4/Phospholipases A2

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


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