Pharmacology and Toxicology

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Charles R. Myers, PhD

Professor
Phone: 414 955-8593
Fax: 414-955-6545
cmyers@mcw.edu

Education:
BS - Carrol College, Waukesha, WI - 1978
MS - Microbiology/Biology, University of Wisconsin, Oshkosh - 1985
PhD - Biological Sciences, University of Wisconsin, Milwaukee - 1987

Dr. Myers' Faculty Collaboration Database

 


Research Interest:

Reductive metal metabolism:

The exposure to certain metals in the environment, water and food supplies, and the workplace can pose a major health hazard. Prime examples include lead poisoning, chromium-related carcinogenesis, and neurologic effects associated with increased intake of metals such as manganese. Our understanding of the metabolism of these metals and their cycling in the environment is limited. It is known, however, that reductive reactions play a role in both the potential toxic effects of these metals and in the mobilization of these metals in the environment. Recent studies in both animals and microbes have indicated a strong role for certain electron-carrier proteins in reductive metal metabolism. Research in my laboratory involves the elucidation of the role of cytochromes and other electron-transporting proteins in reductive metal metabolism.

Reductive Chromium Metabolism:

Exposure to chromium (Cr) compounds is associated with serious damage to internal organs and increased incidence of respiratory tract cancer. The reductive metabolism of Cr(VI) to Cr(III), via reactive intermediates, is thought to play a key role in the cytotoxicity, mutagenicity, and carcinogenicity of Cr. The mechanisms of Cr(VI) reduction in humans are distinct from those reported in rodent models. We are therefore investigating the role of human microsomal enzymes (P450 reductase, cytochrome b5, b5 reductase) in the reduction of Cr(VI) in order to better understand their potential role in mediating cell damage associated with CR(VI) exposure (e.g. free radical attack, lipid peroxidation, DNA strand breaks, etc.).

Reductive Iron and Manganese Metabolism:

Recent studies with a microbial model indicate a strong role for electron-transport proteins in the reductive metabolism of metals such as manganese (Mn) and iron (Fe). Our goals are to examine, in detail, the enzymes responsible for metal reduction in this model system. This will greatly enhance our understanding of how cells interact with metals and of how these processes affect the availability of metals to biological systems. Both biochemical and molecular approaches are being used to elucidate the identity, role, and membrane topology of components required for metal reduction, including quinones, cytochromes, and flavoproteins.


Recent Publications

G. R. Borthiry, W. E. Antholine, B. Kalyanaraman, J. M. Myers, C. R. Myers. 2007. Reduction of hexavalent chromium by human cytochrome b5: generation of hydroxyl radical and superoxide. Free Radic. Biol. Med.42:738–755.

G. R. Borthiry, W. E. Antholine, J. M. Myers, C. R. Myers. 2008. Reductive activation of hexavalent chromium by human lung epithelial cells: generation of Cr(V) and Cr(V)-thiol species. Journal of Inorganic Biochemistry 102: 1449-1462. PMC2497427.

J. M. Myers, W. E. Antholine, C. R. Myers. 2008. Hexavalent chromium causes the oxidation of thioredoxin in human bronchial epithelial cells. Toxicology 246:222-233. PMC2386998

C. R. Myers, J. M. Myers. 2009. The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells.      Toxicology 257: 95-104.

J. M. Myers, C. R. Myers. 2009. The effects of hexavalent chromium on thioredoxin reductase and peroxiredoxins in human bronchial epithelial cells. Free Radic. Biol. Med.47:1477–1485. PMC2767428

Q. Cheng, W. E. Antholine, J. M. Myers , B. Kalyanaraman, E. S. J. Arnér, C. R. Myers. 2010. The selenium-independent inherent pro-oxidant NADPH oxidase activity of mammalian thioredoxin reductase and its selenium-dependent direct peroxidase activities.  J. Biol. Chem. 285:21708-21723. PMC2898413

C. R. Myers, W. E. Antholine, J. M. Myers. 2010. The pro-oxidant chromium(VI) inhibits mitochondrial complex I, complex II, and aconitase in the bronchial epithelium: EPR markers for Fe-S proteins. Free Radic. Biol. Med. 49:1903–1915.

J. M. Myers, W. E. Antholine, C. R. Myers. 2011. The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol. Lett. 201:130–136.

J. M. Myers, W. E. Antholine, C. R. Myers. 2011. The intracellular redox stress caused by hexavalent chromium is selective for proteins that have key roles in cell survival and thiol redox control. Toxicology 281:37–47.

C. R. Myers. 2012. The effects of chromium(VI) on the thioredoxin system: implications for redox regulation. Free Radic. Biol. Med. 52:2091–2107. PMC Journal.

R. D. Bongard, C. R. Myers, B. J. Lindemer, S. Baumgardt, F. J. Gonzalez, M. P. Merker. 2012. Coenzyme Q1 as a probe for mitochondrial complex I activity in the intact perfused hyperoxia-exposed wild-type and Nqo1-null mouse lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 302:L949–L958. PMID: 22268123, PMC Journal.

X. Qi, H. Zhi, A. Lepp, P. Wang, J. Huang, Z. Basir, C. R. Chitambar, C. R. Myers, G. Chen. 2012. p38γ mitogen-activated protein kinase (MAPK) confers breast cancer hormone sensitivity by switching estrogen receptor (ER) signaling from the classical to the non-classical pathway via stimulating ER phosphorylation and c-Jun transcription. J. Biol. Chem. 287:14681–14691.

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