|Luke Szweda, PhD
Free Radical Biology and Aging Research Program
Oklahoma Medical Research Foundation
825 NE 13th Street
Oklahoma City, OK 73104
- Mitochondria exhibit alterations in the rate of oxygen radical production in response to physiological stimuli and during the progression of numerous degenerative disorders including cardiac ischemia/reperfusion and diabetes. Oxygen radicals can alter protein function reversibly, indicating the potential for regulation, or can cause irreversible damage. Our research seeks to define molecular events responsible for changes in mitochondrial free radical production, biochemical mechanisms by which alterations in redox status modulate mitochondrial function, and factors that control the progression from reversible inhibition to irreversible inactivation of protein function. We utilize biophysical, biochemical, and physiological approaches to define targets, mechanisms, and metabolic consequences of oxidative modification. Information gained from these studies is required to delineate pathways and physiological implications of redox regulation and for the development of effective strategies to treat and/or prevent pathophysiological conditions associated with increased oxidative stress.
||Post-Doctoral Fellow - Laboratory of Biochemistry, National Heart, Lung, & Blood Institute, National Institutes of Health, Bethesda, Maryland
||PhD - Biochemistry, Department of Chemistry & Biochemistry, University of California, Los Angeles, CA
||BA - Chemistry, Carleton College, Northfield, MN
Zhang, S.X., Wang, J.J., Dashiti, A., Wilson, K., Zou, M-H., Szweda, L., Ma, J-x., and Lyons, T.J. Pigment Epithelium-derived Factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J Mol Endocrinol, June 27, 2008 [Epub ahead of print].
Wu, M., Chen, Y., Wilson, K., Chirindel, A., Ihnat, M.A., Yu, Y., Boulton, M.E.,Szweda, L, Ma, J-x., and Lyons, T.J., Intra-retinal leakage and oxidation of LDL in diabetic retinopathy (2008) Invest Ophthalmo. Vis. Sci. (In Press).
Martin, C.M., Ferdous, A., Gallardo, T., Humphries, C., Sadek, H. Caprioli, A., Garcia, J., Szweda, L.I., Garry, M.G., and Garry, D.J., HIF-2a transactivates Abcg2 and promotes cytoprotection in cardiac SP cells (2008) Circ. Res. (In Press).
Applegate, M.A., Humphries, K.M., Szweda, L.I., Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid (2008) Biochemistry 47, 473-478.
Matsuzaki, S. and Szweda, L.I., Inhibition of Complex I by Ca2+ Reduces Electron Transport Activity and the Rate of Superoxide Anion Production in Cardiac Submitochondrial Particles (2007) Biochemistry 46, 1350-1357.
Oktay, Y., Dioum, E., Matsuzaki, S., Ding, K., Yan, L-J., Haller, R.G., Szweda, L.I., and Garcia, J.A., HIF-2a null liver mitochondria have reduced frataxin levels and impaired mitochondrial aconitase activity (2007) J. Biol. Chem. 282, 11750-11756.
Lundberg, K.C., and Szweda L.I., Preconditioning prevents loss in mitochondrial function and release of cytochrome c during prolonged ischemia/reperfusion (2006) Arch. Biochem. Biophys. 453, 130-134.
Lashin, O.M., Szweda, P.A., Szweda, L.I., and Romani, A.M., Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart (2006) Free Radic. Biol. Med. 40, 886-96.
Bulteau, A.-L., Lundberg, K.C., Ikeda-Saito, M., Isaya, G., Szweda, L.I., Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion (2005) Proc. Natl. Acad. Sci. USA 102:5987-5991.
Churchill, E.N., Murriel, C.L., Chen, C.H., Mochly-Rosen, D., Szweda, L.I., Reperfusion-induced translocation of dPKC to Cardiac Mitochondria prevents pyruvate dehydrogenase reactivation (2005) Circ. Res. 97:78-85.
Rosca, M.G., Mustata, T.G., Kinter, M.T., Ozdemir, A.M., Kern, T.S., Szweda, L.I., Brownlee, M., Monnier, V.M., Weiss, M.F., Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation (2005) Am. J. Physiol. Renal Physiol. 289:420-430.
Bulteau, A.-L., O’Neill, H.A., Kennedy, M.C., Ikeda-Saito, M., Isaya, G., and Szweda, L.I., Frataxin Acts as an Iron Chaperone Protein to Modulate Mitochondrial Aconitase Activity (2004) Science 305, (5681): 242-245
Sadek, H.A., Szweda, P.A., and Szweda, L.I., Modulation of Mitochondrial Complex I Activity by Reversible Ca2+ and NADH Mediated Superoxide Anion Dependent Inhibition (2004) Biochemistry 43, 8494-8502