Tumour necrosis factor alpha activates a p22phox-based NADH oxidase in vascular smooth muscle.

摘要: Increasing experimental evidence suggests that non-phagocytic cells express a potent superoxide (O2-.)-producing NADH oxidase might be related to the phagocytic NADPH oxidase. Here we show cytokine tumour necrosis factor alpha (TNF-alpha) activates, in time- and dose-dependent manner, O2-.-producing cultured rat aortic smooth-muscle cells. Dose-response experiments for showed an upward shift of curve TNF-alpha-treated cells, suggesting TNF-alpha increased amount available enzyme. Using anti-sense transfection technique, further demonstrate molecular identity this includes p22(phox) (the subunit cytochrome b558 part electron transfer component oxidase), which recently cloned from vascular cell cDNA library. In addition, prolonged treatment with p22phox mRNA expression without affecting stability, only when transcriptional activity was intact. These findings identify p22phox-containing as source cytokine-induced free radical production clarify some mechanisms involved regulation activity.