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Role of NOX4 in Superoxide Production Stimulated by H + Efflux in mTAL of SS Rat
Author(s) -
Zheleznova Nadezhda,
O'Connor Paul,
Cowley Allen
Publication year - 2015
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.29.1_supplement.963.10
Subject(s) - superoxide , nox4 , nadph oxidase , chemistry , biochemistry , efflux , medicine , endocrinology , reactive oxygen species , biology , enzyme
Renal medullary thick ascending limb (mTAL) tubular segments produce superoxide mostly derived from NADPH oxidases (NOXs).Superoxide production is augmented in Dahl salt‐sensitive (SS) rats and contributes to the development of hypertension in these animals. We have shown that the voltage‐gated proton channel Hv1 contributes to superoxide production in the mTAL of the SS rat during proton efflux however, as Hv1 itself does not produce superoxide, the molecular source of superoxide radicals remains unknown. We hypothesize that NOX4 might be involved in Hv1‐dependent superoxide production during proton efflux in mTAL. To test this, mTAL superoxide production (ΔEth/ΔDHE ratio) was compared between control SS and mutant SS Nox4‐/‐ rats (where Nox4 gene was knocked out in SS genetic background using zinc finger nuclease (ZFN) technique) in response to cellular acidification (using an NH 4 Cl loading/removal; 20 mmol/L). It was found that increase in superoxide production after acidification in microdissected mTAL from SS rats was blunted nearly 30% in mTAL isolated from SS Nox4‐/‐ mutant rats. We conclude that Hv1 dependent O 2 − · production following mTAL cellular acidification is partially dependent on the presence of NADPH oxidase 4 (NOX4) although NOX4 may not be the source of O 2 − · production (HL116264)