Nrf2 (nuclear factor erythroid-2–related factor 2) is a stress-responsive transcription factor that plays a critical role in the maintenance of intracellular redox homeostasis. In response to oxidant stress, Nrf2 signaling upregulates multiple downstream antioxidant genes and phase II detoxification enzymes, including NADPH dehydrogenase quinone 1, thioredoxin reductase, heme oxygenase-1, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, Nrf2 is likely to increase anti-oxidant gene expression in response to cellular stress that occurs during bouts of exercise. Although we have found that Nrf2 expression is increased in skeletal and cardiac muscle in response to regular treadmill exercise training, little is known about the role of Nrf2 in exercise training-induced adaptations of the blood vessels within skeletal and cardiac muscle. We have previously documented that exercise training induces upregulation of anti-oxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, in the endothelium and smooth muscle of blood vessels in skeletal and cardiac muscle. In our current studies we are investigating the effects of Nrf2 deletion on adaptations of the blood vessels in skeletal and cardiac muscle in male and female rats. Our data thus far indicate that deletion of Nrf2 abrogates the beneficial adaptations of blood vessels that normally occur in response to treadmill exercise training. We are currently investigating the cellular mechanisms that underlie this effect of Nrf2 deletion, with particular emphasis being placed on regulation of expression of anti-oxidant enzymes and potassium channels. The overall goal of this research is to understand the role of Nrf2 signaling in modulating adaptations of the endothelium and vascular smooth muscle that occur in response to physiological stress induced by bouts of exercise.
Research Skills: A post-doctoral scholar in the Delp lab will obtain research skills and methodology to assess all aspects of adaptation in the microvasculature. We perform assessment of microvascular reactivity using an isolated vessel preparation and we assess mRNA and protein expression in single blood vessels. In addition, post-doctoral scholars will learn methods for assessing angiogenesis and adaptation of blood vessel networks. All of these microvascular techniques are performed in the context of whole models of aging and exercise training.
Career Skills: A post-doctoral scholar in my lab will receive mentoring in writing of manuscripts and grant applications. In addition, post-doctoral scholars are encouraged to attend national meetings sponsored by the American Physiological Society, the Microcirculatory Society, and the American College of Sports Medicine. My goal is to prepare trainees for an independent research career. During their time in my lab, I hope to help them gain funding (K award) that will transfer to their own career.