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NADPH oxidase upregulates intermediate‐conductance Ca2+ ‐ activated K+ channels (KCa3.1) in coronary smooth muscle
Author(s) -
Gole Hope,
Bowles Douglas
Publication year - 2011
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.25.1_supplement.1026.16
Subject(s) - nox4 , nox1 , nadph oxidase , downregulation and upregulation , superoxide , oxidative stress , gene isoform , chemistry , endocrinology , medicine , microbiology and biotechnology , biology , biochemistry , enzyme , gene
Oxidative stress is known to play a role in cardiovascular disease including atherosclerosis. While several ROS may be involved, NADPH oxidase appears to play a key role. Studies have shown VSMC phenotypic modulation is critical to the development of atherosclerotic plaques. KCa3.1 is one mechanism by which increased VSMC proliferation and migration occurs. Our objective was to determine if NADPH oxidase plays a role in KCa3.1 upregulation. In coronary SMCs, bFGF increased superoxide (O2.‐) production; increased KCa3.1 mRNA levels ~2.5 fold, protein expression ~2.5 fold, and channel activity ~4.0 fold; and increased AP‐1 activity ~2.0 fold. Apo inhibited the bFGF increase in O2.‐, KCa3.1 message and activity, and AP‐1 activity. Coronary smooth muscle expressed all four cardiovascular Nox isoforms (Nox1,2,4, and 5) with Nox4 being the predominant isoform. bFGF decreased Nox1,2, and 4 message, while Apo increased message of all four isoforms. Nox2 and Nox4 siRNA did not affect KCa3.1 message response to bFGF or Apo. Our findings provide novel evidence that NADPH oxidase contributes to VSMC phenotypic modulation through AP‐1 transcriptional upregulation of KCa3.1.