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Hydrogen peroxide derived from Nox‐2 mediates protein kinase C‐induced contraction of bovine coronary artery and mouse aorta
Author(s) -
Gupte Sachin A,
Hintze Thomas H,
Wolin Michael S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a724-b
Subject(s) - protein kinase c , superoxide , nadph oxidase , chemistry , contraction (grammar) , phorbol , oxidase test , nad(p)h oxidase , medicine , reactive oxygen species , aorta , endocrinology , kinase , biochemistry , enzyme
Activation of protein kinase C (PKC) is known to stimulate NAD(P)H oxidase‐derived superoxide and hydrogen peroxide (H2O2). In this study, we investigated which oxidase participates in increasing H2O2 levels and force generation by PKC activation. Stimulation of PKC by phorbol‐12,13‐dibutyrate (PDBu: 10 uM) increased superoxide levels by 4‐fold and force generation to levels generated by 30 mM KCl in endothelium‐removed bovine coronary arteries (BCA). Force generation elicited by PDBu was partially Ca2+‐dependent, because PDBu‐induced contraction was suppressed by 45.6% in Ca2+ free Krebs solution. In contrast, superoxide generation by PKC activation was Ca2+‐independent. However, PKC‐elicited BCA contraction was partially inhibited (42%) by a NADPH oxidase inhibitor, gp91dstat (50 uM). Moreover, gp91dstat inhibited PDBu‐elicited contraction of Wild‐type aorta by 85%; whereas PDBu did not induce contraction in gp91phox knockout mice aorta. Therefore, our data indicate that H2O2 derived from Nox‐2 mediates PKC‐induced contraction of bovine coronary artery and mouse aorta. (Supported by NIH grants HL 31069, HL43023, HL66331).