Rodney C. Baker, Ph.D. Professor Guyton 323 (601) 984-1620 RBaker@pharmacology.umsmed.edu

I am interested in the mechanisms by which disruption of phospholipid metabolism contributes to the cytotoxicity of alcohols, specifically short chain alcohols such as ethanol, methanol, and butanol. Alcohols are toxic to most cells although the clinically important symptoms are unique to each alcohol. Ethanol is associated with cancer, cardiovascular disease, liver damage and brain damage. Methanol has selective toxic actions on the retina and optic nerve and butanol is a general cytotoxic compound.

Chronic ethanol use if recognized as a major health problem and is one of the leading contributors to mental disease and liver disease, all of which are characterized by a loss of cells in the affected tissues. The studies in this laboratory evaluate the effect of alcohols on phospholipid metabolism and the relationship of the alcohol-induced changes to cell death. The unique phospholipase D product, phosphatidylethanol, which is produced in the presence of ethanol, induces apoptosis in lymphocytes, inhibits DNA synthesis in brain cells, and accelerates cell differentiation in lymphoid cells. Phospholipase D activity in the presence of other short chain alcohols catalyzed the synthesis of the corresponding phosphatidylalcohol, and these compounds may contribute to the toxicity of alcohol solvents and fuels.

Selected Publications

Baker, R. C., Tucker, M. and Clay, K. C. Ethanol inhibits zymosan stimulate and enhances non stimulated platelet-activating factor production in a clonal macrophage cell line. J. Pharmacol. Exp. Ther. 252: 1028-1033, 1990.

Tomita-Yamaguch, M., Babich, J. E., Baker, R. C. and Santoro, T. J. Incorporation distribution and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice. J. Expt. Med. 171: 787-800, 1990.

Aroor, A.R.and Baker, R.C. Ethanol-induced apoptosis in human HL-60 cells. Life Sci. 61: 2345-2350, 1997.

Aroor, A.R. and Baker, R.C. Ethanol inhibition of phagocytosis and superoxide anion production by microglia. Alcohol 15: 277-280, 1998.

Mamoon, A.M., Baker, R.C. and Farley, J.M. Activation of phospholipase D in porcine tracheal smooth muscle: role of phosphatidylinositol 3-kinase and RhoA activation. Europ. J. Pharmacol. 433: 7-16, 2001.

Couch, D.B. and Baker, R.C. Ethanol-enhanced cytotoxicity of alkylating agents. Alcoholism: Clin. Exper. Res. 26: 381-385, 2002.

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