Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Bahie Abou-Donia

Bahie Abou-Donia, Ph.D.
Professor of Pharmacology and Cancer Biology
Professor of Neurobiology

Duke University Medical Center
C173A LSRC
Box 3813
Durham, NC 27710

Phone: 919-684-2221
E-mail: aboud001@mc.duke.edu

Research Interests

Some chemicals induce neurodegenerative disorders characterized by Wallerian-type degeneration of the central and peripheral nervous systems. An example is organophosphorus ester-induced delayed neurotoxicity (OPIDN). OPIDN is a distal axonopathy of the peripheral and central nervous systems and is characterized by axonal swellings containing cytoskeletal protein aggregates. A pathognomonic of OPIDN is an aberrant increased autophosphorylation of calcium/calmodulin kinase II (CaM kinase II) and enhanced phosphorylation of cytoskeletal proteins, i.e., MAP's, tubulin, neurofilament triplet proteins and myelin basic protein. Our results suggest that in OPIDN, hyperphosphoryl-ation of cytoskeletal proteins and axonal swelling are causally linked. Hyperphosphorylation of cytoskeletal proteins decreases their transport rate down the axon relative to their rate of entry into the axon, thus leading to their accumulation. Consistent with this hypothesis is the finding of the anomalous accumulation of phosphorylated neurofilament aggregates in the central and peripheral axons of hens treated with the delayed neurotoxicant tri-s-cresyl phosphate (TOCP).

Publications

Abou-Donia, M.B., K.R. Wilmarth, K.F. Jensen, F.W. Oehme, and T.L. Kurt (1996). Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: Implications of Gulf War chemical exposures. J. Toxicol. Environ. Health., 48: 35-56.

Lanning, C.L., R.L. Fine, J.J. Corcoran, H.M. Ayad, R.L. Rose, and M.B. Abou- Donia (1996). Tobacco budworm p-glycoprotein: biochemical characterization and its involvement in pesticide resistence. Biochem. Biophys. Acta., 1291: 155-162.

Abou-Donia, M.B., K.R. Wilmarth, A.A. Abdel-Rahman, K.F. Jensen, F.W. Oehme, and T.L. Kurt (1996). Increased neurotoxicity following simultaneous exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundam. Appl. Toxicol., 34: 201-220.

Gupta, R.P., W.W. Lin, and M.B. Abou-Donia (1999). Enhanced mRNA expression of neurofilament subunits in the brain and spinal cord of dissopropyl phosphorofluoridate-treated hens. Biochem. Pharmacol. 571245-1251.

Gupta, R.P., and M.B. Abou-Donia (1999). Tau phosphorylation by diisopropylphosphorafloridate (DFP)-treated hen brain supernatant inhibits its binding with microtubules: role of Ca²+/Calmodulin-dependent protein kinase II in tau phorphorylation. Arch. Biochem. Biophys. 813:32-43.

Abu-Qare, A. W. A.A. Abdel-Rahman, A.M. Kishk, and M.B. Abou-Donia (2000) Placental transfer and pharmacokinetics of a single dermal dose of r4C]methyl parathion in rats. Toxicol. Sci. 53: 5-12.

Abou-Donia, M.B., A.A. Abdel-Rahman, A.A. Kishk, D. Walker, B.J. Markwiese, S.K. Achesion, K.E. Reagan, S.Swartzwelder, and K.F. Jensen. (2000). Neurotoxicity of ethyl methacrylate. J. ToxicolEnviron.Health. 59: 97-118.

Abou-Donia, M.B. and L.K. Garrettson (2000). Detection of neurofilament autoantibodies in human serum following chemically induced neurologic disorder: A case study. Environ. Epidem. Toxicol. 2:37-41.

Damodaran, T.V. and M.B. Abou-Donia (2000). Alterations in levels of MRNAs coding for glial fibrillary acidic protein (GFAP) and vimention genes in the central nervous system of hens trates with diisopropyl phosphorofluoridate (DFP). Neurochem. Res. (in press)

Khan W.A., A.M. Dechkovskaia, E.A. Herrick, K.H. Jones and M.B. Abou-Donia (2000). Acute sarin exposure causes differential regulations of choline acetyl transference, acetylcholinesterase, and acetylcholine receptors in the central nervous system of rats. Toxicol. Sci. (in press)

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