Document Detail

Regulation of adrenal aldosterone production by serine protease prostasin.
MedLine Citation:
PMID:  20204133     Owner:  NLM     Status:  MEDLINE    
A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells). Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC) inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation.
Takehiro Ko; Yutaka Kakizoe; Naoki Wakida; Manabu Hayata; Kohei Uchimura; Naoki Shiraishi; Taku Miyoshi; Masataka Adachi; Shizuka Aritomi; Tomoyuki Konda; Kimio Tomita; Kenichiro Kitamura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-02
Journal Detail:
Title:  Journal of biomedicine & biotechnology     Volume:  2010     ISSN:  1110-7251     ISO Abbreviation:  J. Biomed. Biotechnol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-05-25     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  101135740     Medline TA:  J Biomed Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  793843     Citation Subset:  IM    
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan.
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MeSH Terms
Adrenal Cortex / drug effects,  enzymology,  metabolism*
Aldosterone / biosynthesis*,  genetics
Aldosterone Synthase / biosynthesis,  genetics,  metabolism
Angiotensin II Type 1 Receptor Blockers / pharmacology
Calcium Channel Blockers / pharmacology
Cell Line
Dihydropyridines / pharmacology
Gene Expression Regulation
Gene Silencing
Nitrophenols / pharmacology
Organophosphorus Compounds / pharmacology
Promoter Regions, Genetic
Receptors, Proteinase-Activated / genetics,  metabolism
Recombinant Proteins / pharmacology
Serine Endopeptidases / genetics,  metabolism*,  pharmacology
Tetrazoles / pharmacology
Valine / analogs & derivatives,  pharmacology
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Calcium Channel Blockers; 0/Dihydropyridines; 0/Nitrophenols; 0/Organophosphorus Compounds; 0/Receptors, Proteinase-Activated; 0/Recombinant Proteins; 0/Tetrazoles; 111011-53-1/efonidipine; 137862-53-4/valsartan; 52-39-1/Aldosterone; 7004-03-7/Valine; EC Synthase; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/prostasin

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