TY - JOUR A2 - Chai, Karl AU - Ko, Takehiro AU - Kakizoe, Yutaka AU - Wakida, Naoki AU - Hayata, Manabu AU - Uchimura, Kohei AU - Shiraishi, Naoki AU - Miyoshi, Taku AU - Adachi, Masataka AU - Aritomi, Shizuka AU - Konda, Tomoyuki AU - Tomita, Kimio AU - Kitamura, Kenichiro PY - 2010 DA - 2010/03/02 TI - Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin SP - 793843 VL - 2010 AB - 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. SN - 2314-6133 UR - https://doi.org/10.1155/2010/793843 DO - 10.1155/2010/793843 JF - Journal of Biomedicine and Biotechnology PB - Hindawi Publishing Corporation KW - ER -