Medicine and Health Sciences Commons^™

The Nad(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation Of H202 And Plays An Integral Role In Insulin Signal Transduction, Kalyankar Mahadev, Hiroyuki Motoshima, Xiangdong Wu, Jean Marie Ruddy, Rebecca S. Arnold, Guangjie Cheng, J. David Lambeth, Barry J. Goldstein

Department of Medicine Faculty Papers

Insulin stimulation of target cells elicits a burst of H₂O₂ that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative …