Free radicals are formed when the body uses oxygen to make energy, to process foreign particles, like drugs, even when we encounter sunlight or radiation. Sometimes, when free radicals react with the body’s tissues, damage can occur, leading to heart disease, cancer and many conditions associated with aging.
In my lab, we study the damage that happens when free radicals interact with cells and try to observe how cells protect themselves or change themselves in the process. We have learned that sometimes the body’s reaction to the free radicals, rather than the free radicals themselves, can cause the most damage.
Some cells have the ability to adjust to free radical damage and function normally, or even benefit from the interaction. Other cells see little or no damage from free radicals, while some simply shut down or die.
In heart disease, certain white blood cells often react to free radicals by transforming themselves into “foam” cells. Those cells can lead to atherosclerosis, an inflammatory disease that clogs blood vessels and causes heart disease.
Our goal is to understand these changes so we can use them to our benefit. By identifying the triggers that can either increase good cell responses or decrease bad ones, we may learn ways to prevent many kinds of human disease.
There are two primary activities in my laboratory: characterizing changes in protein expression in hearts and mitochondria from mice that are consuming a high-fat diet and characterizing the sites and chemical structure of oxidant-damaged proteins. A unique aspect of my experiments is the use of mass spectrometry to sequence and characterize proteins. These types of experiments are broadly referred to a proteomics.
In the first area of investigation, we use a proteomic approach – gel electrophoresis and quantitative mass spectrometry – to identify proteins that are differentially expressed in the heart and mitochondria. The general hypothesis being tested in this work is that the high fat diet produces a chronic oxidative stress that alters heart and mitochondrial function through changes in protein expression. Our goal is to discover previously unidentified or unstudied proteins that help drive the progression of the diet-induced heart failure.
In the second area of investigation, we use tandem mass spectrometry to characterize the site and structure of oxidative modifications to proteins. One theory of how oxidative stress affects cells is that key proteins become modified in a manner that alters their function. Our goal is to trace the specific structures that are characterized to new information about the oxidation reactions leading to those modifications and the link between those modifications and cell/tissue damage.
B.S. Chemistry, James Madison University, Harrisonburg, VA, 1982
Ph.D. Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 1986
Postdoc, Clinical Chemistry, University of Virginia, Charlottesville, VA, 1986-1988
American Society for Mass Spectrometry
American Society for Biochemistry and Molecular Biology
Society for Free Radical Biology and Medicine
Joined OMRF Scientific Staff in 2008.
Deepa SS, Pharaoh G, Kinter M, Diaz V, Fok WC, Riddle K, Pulliam D, Hill S, Fischer KE, Soto V, Georgescu C, Wren JD, Viscomi C, Richardson A, Van Remmen H. Lifelong reduction in complex IV induces tissue-specific metabolic effects but does not reduce lifespan or healthspan in mice. Aging Cell. 2018 Apr 25:e12769. Epub ahead of print. PMID: 29696791
Ahn B, Pharaoh G, Premkumar P, Huseman K, Ranjit R, Kinter M, Szweda L, Kiss T, Fulop G, Tarantini S, Csiszar A, Ungvari Z, Van Remmen H. Nrf2 deficiency exacerbates age-related contractile dysfunction and loss of skeletal muscle mass. Redox Biol. 2018 Apr 6; 17:47-58. Epub ahead of print. PMID: 29673700
Schafer C, Young ZT, Makarewich CA, Elnwasany A, Kinter C, Kinter M, Szweda LI. Coenzyme A-mediated degradation of pyruvate dehydrogenase kinase 4 promotes cardiac metabolic flexibility after high-fat feeding in mice. J Biol Chem. 2018 May 4;293(18):6915-6924. Epub 2018 Mar 14. PMID: 29540486
Fu Y, Kinter M, Hudson J, Humphries KM, Lane RS, White JR, Hakim M, Pan Y, Verdin E, Griffin TM. Aging Promotes SIRT3-dependent Cartilage SOD2 Acetylation and Osteoarthritis. Arthritis Rheumatol. 2016 Feb 11. [Abstract]
Walsh ME, Bhattacharya A, Sataranatarajan K, Qaisar R, Sloane L, Rahman MM, Kinter M, Van Remmen H. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell 2015. [Abstract] EPub
Fernandes J, Weddle A, Kinter CS, Humphries KM, Mather T, Szweda LI, Kinter M. Lysine acetylation activates mitochondrial aconitase in the heart. Biochemistry 2015. [Abstract] EPub
Kinter CS, Lundie JM, Patel H, Rindler PM, Szweda LI, Kinter M. A Quantitative proteomic profile of the Nrf2-mediated antioxidant response of macrophages to oxidized LDL determined by multiplexed selected reaction monitoring. PLoS One 7:e50016, 2012. [Abstract]
Rindler PM, Plafker SM, Szweda LI, Kinter M. High dietary fat selectively increases catalase expression within cardiac mitochondria. J Biol Chem 288:1979-1990, 2013. [Abstract]
Conway JP, Kinter M. Proteomic and transcriptomic analyses of macrophages with an increased resistance to oxidized low density lipoprotein (oxLDL)-induced cytotoxicity generated by chronic exposure to oxLDL. Mol Cell Proteomics 4:1522-1540, 2005. [Abstract]
Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7572
Fax: (405) 271-1437