Transcription Factors

Oxygen intermediates regulate numerous cardiovascular-related genes including adhesion molecules that control inflammatory cell recruitment, antioxidant enzymes that regulate ROS interactions with signaling systems, NOS, and vasoactive agents. Modulation of gene expression by oxidative stress occurs primarily through the redox-regulation of transcription factors, such as NFkB, AP-1 and HIF-1.87,90 Activation of NFkB, AP-1, and HIF-1 is induced by ROS, probably through redox modification of reactive cysteines.90 Upstream kinase(s) and or phosphatase(s) prone to thiolation or oxidation of SH groups are at present considered the best candidates mediating the redox regulation of transcription factors. In particular Redox-factor-1

(Ref-1) is an important activator of AP-1, NFkB, and p53 tumor suppressor protein.91 Thioredoxin, an enzyme involved in the repair of oxidatively damaged proteins, suppresses NFkB, yet activates AP-1.92 This phenomenon may act as a compensatory, regulatory mechanism in cells predisposed to oxidative stress. Increased activation of vascular NFkB and AP-1 and associated inflammatory and mitogenic responses have been demonstrated in hypertensive rats.65 These actions have been attributed, in part, to increased oxidative stress.

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