Reactive oxygen and nitrogen species are part of normal metabolism and play prominent roles in cardiovascular (patho)physiology. These reactive species and their secondary products (e.g., oxidized lipids) covalently modify proteins, thereby modulating enzyme function or eliciting redox signaling. Mitochondria, in particular, are both sources and targets of these reactive species and are themselves critical regulators of myocardial and vascular injury. Therefore, the general goal of ongoing studies in our laboratory is to understand how mitochondrial damage due to oxidants regulates cardiovascular health and disease. Specifically, we are focusing on how diabetes affects the function and physiology of mitochondria, with an emphasis on their role in causing myocardial insulin resistance. This approach involves the use and development of techniques to monitor cellular bioenergetics in the heart and vasculature. The long-term objective is to apply knowledge gained from these studies to cultivate new understanding of how to target mitochondria or mitochondria-related signaling to prevent or ameliorate cardiovascular diseases caused by the diabetic phenotype.
- Sansbury BE, Cummins TD, Tang Y, Hellmann J, Holden CR, Harbeson MA, Chen Y, Patel RP, Spite M, Bhatnagar A,Hill BG..Overexpression of endothelial nitric oxide synthase prevents diet-induced obesity and regulates adipocyte phenotype.Circ Res.2012 Oct 12;111(9):1176-89. doi: 10.1161/CIRCRESAHA.112.266395. Epub 2012 Aug 14
- Ingram KH, Hill H, Moellering DR, Hill BG, Lara-Castro C, Newcomer B, Brandon LJ, Ingalls CP, Penumetcha M, Rupp JC, Garvey WT. Skeletal muscle lipid peroxidation and insulin resistance in humans.J Clin Endocrinol Metab. 2012 Jul;97(7):E1182-6. Epub 2012 Apr 11.
- Hill BG, Dranka BP, Bailey SM, Lancaster JR Jr, Darley-Usmar VM. What part of NO don't you understand? Some answers to the cardinal questions in nitric oxide biology.J Biol Chem. 2010 Jun 25;285(26):19699-704. Epub 2010 Apr 21.
- Cummins TD, Higdon AN, Kramer PA, Chacko BK, Riggs DW, Salabei JK, Dell'italia LJ, Zhang J, Darley-Usmar VM, Hill BG.Utilization of fluorescent probes for the quantification and identification of subcellular proteomes and biological processes regulated by lipid peroxidation products.Free Radic Biol Med.2012 Aug 23. pii: S0891-5849(12)00503-5. doi: 10.1016/j.freeradbiomed.2012.08.014.
- Sansbury BE, Riggs DW, Brainard RE, Salabei JK, Jones SP, Hill BG. Responses of hypertrophied myocytes to reactive species: implications for glycolysis and electrophile metabolism.Biochem J. 2011 Apr 15;435(2):519-28.
- Hill BG, Dranka BP, Zou L, Chatham JC, Darley-Usmar VM. Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal.Biochem J. 2009 Oct 23;424(1):99-107.
- Hill BG, Awe SO, Vladykovskaya E, Ahmed Y, Liu SQ, Bhatnagar A, Srivastava S. Myocardial ischaemia inhibits mitochondrial metabolism of 4-hydroxy-trans-2-nonenal.Biochem J. 2009 Jan 15;417(2):513-24.
- West MB, Rokosh G, Obal D, Velayutham M, Xuan YT, Hill BG, Keith RJ, Schrader J, Guo Y, Conklin DJ, Prabhu SD, Zweier JL, Bolli R, Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition.Circulation. 2008 Nov 4;118(19):1970-8. Epub 2008 Oct 20.
- Jones SP, Zachara NE, Ngoh GA, Hill BG, Teshima Y, Bhatnagar A, Hart GW, Marbán E. Cardioprotection by N-acetylglucosamine linkage to cellular proteins.Circulation. 2008 Mar 4;117(9):1172-82. Epub 2008 Feb 19.
- West MB, Hill BG, Xuan YT, Bhatnagar A. Protein glutathiolation by nitric oxide: an intracellular mechanism regulating redox protein modification.FASEB J. 2006 Aug;20(10):1715-7. Epub 2006 Jun 29.