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Daniel Cervantes Laurean, Assistant Professor
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Phone: (605) 688-6171
E mail Dr. Daniel Cervantes
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Resume/Professional Information
Research Interests
protein damage induced by oxidative stress in aging, diabetes and cancer
Topics
Measurements of biomarkers of protein damage and the activation of biological defense mechanism against oxidative stress
Research Description
Biomedical research requires a multidisciplinary effort in which biochemistry is an important and crucial contributor to this effort. The tools of biochemistry are used to first understand and then to contribute in either prevent or cure human disease. Oxidative stress results from molecular damage to tissue macromolecules, such as proteins, lipids, and DNA. My laboratory is focused in particular with protein damage in which. reactive oxygen (ROS) and reactive carbonyl species (RCS) are key intermediates of oxidative and carbonyl stress leading to cellular damage and disruption of genomic integrity. Formation of ROS and RCS results from various endogenous and exogenous sources, e.g. exposure to solar light, xenobiotics, oxygen metabolism, and hyperglycemia. Protein damage can be caused by reactive carbonyl species (RCS) such as glyoxal and methylglyoxal, which is formed by degradation of lipid peroxidation products, early protein glycation adducts and by side reaction products of glycolysis, and oxidation of serine at inflammation sites.
Glyoxal and methylglyoxal are RCS that reacts non-enzymatically with amino groups of lysine to form intermediates that lead to formation of advanced glycation end products (AGEs), such as Ne-carboxymethylysine (CML) and Ne-carboxyethylysine (CEL). CML and CEL, increased in pathological conditions of skin such as actinic elastosis, diabetes complications and the aging process, has been used to monitor intracellular glyoxal and methylglyoxal oxidative stress. Oxidatively damaged proteins are degraded by the 20S proteasomal system activity in the nucleus and the cytoplasm in an ATP and ubiquitin independent manner. The nuclear proteasome activity in cancer cells is dramatically higher than normal cells. The increase activity of the proteasome in cancer cells is presumptively to cope with increased oxidative stress generated by higher metabolic activity. Recently it has been shown that hydrogen peroxide activates the nuclear proteasomal activity in leukemia cells in a poly-ADP-ribose polymerase dependent manner. Also the translocation of the cytoplasmic proteasome to the nucleus has been shown to occur in oxidative stress conditions and in the transport of chemotherapeutic cancer agents such anthracycline and an adriamycin derivative.
In order to test the effect of RCS in the nuclear and total proteasome activity in normal and cancer cells we used glyoxal and methylglyoxal in human HaCat keratinocytes and fibroblasts. This is with the long goal to maximize protective cellular responses and find inhibitors of glycation to delay the deleterious effects of protein and DNA damage involved in a variety of diseases, which include cancer, diabetes complications, and the ageing process.
Publications
Daniel Cervantes Laurean, Michael 1. Roberts, Elaine L. Jacobson. (2004) "Nuclear proteasome activation and degradation of glycated histones in human keratinocytes following glyoxal treatment." In press (Free Radical Biology and Medicine)
Bourgeois, C., Cervantes Laurean, D., & Moss, 1. (2004) "Niacin" in Modern Nutrition in Health and Disease (Shils, M.E., Olson, J. A., Shike, M., & Ross A. C. Eds.) In print
Wondrak, G.T., Roberts, MJ., Cervantes Laurean, D., Jacobson, M.K., and Jacboson, E.L (2003). "Proteins of the Extracellular Matrix are Sensitizers of Photooxidative Stress in Human Skin Cells" J Invest Dermatol121, 578-586.
Roberts, M. J., Wondrak, G. T., Cervantes Laurean, D., Jacobson, M. K., and Jacobson, E. L. (2003) "DNA Damage by Carbonyl Stress in Human Skin Cells" Mutation Research 522, 45-56.
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