Arthur W. Bull
Title: Professor Biochemistry
Office: 253 Science and Engineering Building
Phone: (248) 370-2347
Ph.D., Wayne State University
Dr. Bull's group is actively investigating the metabolic disposition and biological activity of oxidized derivatives of linoleic acid. The major pathway for oxygenation of linoleic acid involves production of 13-hydroperoxyoctadecadienoic acid by the action of lipoxygenases or cyclooxygenases. This is followed by reduction of the hydroperoxy fatty acid to the hydroxy derivative (13-HODE) and the subsequent dehydrogenation of 13-HODE to the 2,4-dienone 13-OXO. Research efforts are currently focused in two areas related to this metabolic pathway. One area of emphasis involves unraveling the biochemical contribution of 13-HODE dehydrogenase to cellular regulation. A second area of interest involves identification of crucial cellular targets interacting with key metabolites of oxidized linoleic acid. Both chemical and biochemical techniques are employed to address these questions and elucidate these pathways.
A second major area of interest involves attempts to elucidate the mechanism by which conjugated derivatives of linoleic acid, known as CLAs, inhibit mammary tumorigenesis. The CLAs have been shown to be non-toxic inhibitors of both initiation and post initiation events during mammary carcinogenesis. Our emphasis in these investigations involves an examination of the potential modulation of the oxidative metabolism of polyunsaturated fatty acids by CLA. Again, identification of biological targets and the elucidation of metabolic pathways available to CLA are major goals of these NIH-supported investigations.
Blackburn, M.L., Podgorski, I., and Bull, A.W. Specific Protein Targets of 13-Oxooctadecadienoic Acid (13-OXO) and Export of the 13-OXO - Glutathione Conjugate in HT-29 Cells. Biochem. Biophys. Acta 1440: 225-234 (1999).
Jude, A.R., Little, J.M., Bull, A.W., Podgorski, I.P., and Radominska-Pandya, A. 13-Hydroxy and 13-oxooctadecadienoic acids: Novel substrates for human UDP-glucuronosyltransferases. Drug Metab. Disp. 29: 652-655 (2001).
Bull, A.W., Geno, J.L., Leach, A.R., and Podgorski, I. The role of glutathione-S-transferases in the metabolic disposition of bioactive linoleic acid oxidation products. Chem. Biol. Interactions 133: 237-239 (2001).
Bulgarella, J.A, Patton, D., and Bull, A.W. Modulation of Prostaglandin H Synthase Activity by Conjugated Linoleic Acid and Specific CLA Isomers. Lipids 36: 407-412 (2001).
Podgorski, I., and Bull, A.W. Energy Dependent Export of the 13-oxooctadecadienoic acid-glutathione conjugate from HT-29 cells and plasma membrane vesicles. Biochim. Biophys. Acta 1553: 55-65 (2001).
Bull, A.W., Seeley, S.K., Geno, J., and Mannervik, B. Conjugation of the Linoleic Acid Oxidation Product, 13-oxooctadeca-9,11-dienoic Acid, A Bioactive Endogenous Substrate for Mammalian Glutathione Transferase. Biochim. Biophys Acta1571: 77-82 (2002).
Liboff, A.R., Cherng, S., Jenrow, K.A., and Bull, A. Calmodulin-Dependent cyclic nucleotide phosphodiesterase activity is altered by 20 µT magnetostatic fields. Bioelectromagnetics 24: 32-38 (2003).
Bull, A.W. The role of peroxisome proliferator-activated receptor g in colon cancer and inflammatory bowel disease.Arch. Pathol. Lab Med 127: 1121-1123 (2003).
Bull, A.W., Steffensen, K.R., Leers, J., and Rafter, J.J. Activation of PPAR g in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR g. Carcinogenesis 24: (in press) 2003