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Autocrine Action of NAD(P)H Oxidase‐Derived Extracellular Superoxide in Coronary Arterial Myocytes
Author(s) -
Zhang Fan,
Chen QiZheng,
Yi Fan,
Li PinLan
Publication year - 2007
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.21.6.a797-a
Subject(s) - extracellular , autocrine signalling , nad+ kinase , chemistry , superoxide , nadph oxidase , nad(p)h oxidase , nicotinamide adenine dinucleotide phosphate , biochemistry , ryanodine receptor , apocynin , oxidase test , intracellular , pharmacology , microbiology and biotechnology , receptor , reactive oxygen species , biology , enzyme
Our recent studies have indicated that there is an autocrine/paracrine pattern of superoxide production through NAD(P)H oxidase in coronary arterial myocytes (CAMs). The present study determined whether extracellular O 2 ·− could serve as an autocrine factor to activate intracellular Ca 2+ signaling pathway and explored related underlying mechanisms. Using a newly established dual fluorescence microscopic imaging technique, We found that M 1 ‐receptor agonist oxotremorine (Oxo) simultaneously increased the extracellular O 2 ·− production and [Ca 2+ ] i, , which were significantly attenuated by addition of superoxide dismutase (SOD) and catalase into the bath solution. NAD(P)H oxidase inhibitor, apocynin also inhibited this response of CAMs to Oxo. When ADP‐ribosyl cyclase inhibitor ‐ nicotinamide, RyR/Ca 2+ release channel antagonists ‐ ryanodine or cADPR antagonist ‐ 8‐Br‐cADPR was added into the bath solution, Oxo‐induced increase in [Ca 2+ ] i was abolished, while extracellular O 2 ·− production remained. Furthermore, introduction of cADPR into CAMs by ultrasound microbubbles increased [Ca 2+ ] i, ,but it had no effect on extracellular O 2 ·− production. These results provide direct evidence that extracellular O 2 ·− derived from NAD(P)H oxidase contributes to Ca 2+ activation of CAMs through its autocrine action on cADPR signaling pathway (Supported by NIH grants HL057244 and HL075316).