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Professor Glenn Dryhurst

Office: CHB 313
Phone: (405) 325-9013
Email: gdryhurst@ou.edu

Glenn Dryhurst

  • George Lynn Cross Research Professor.
  • B.Sc. (University of Aston in Birmingham, England) 1962
  • Ph.D. (University of Birmingham, England) 1965

  • Research Associate (University of Michigan) 1965-1967
  • Young Author Prize, The Electrochemical Society, 1969.
  • George Lynn Cross Research Professor, 1983.
  • Fulbright Senior Professor Award, 1987-1988, Konstanz University, Germany.
  • Oklahoma Chemist Award, American Chemical Society, 1989.
  • Heyrovsky Centennial Medal, Czechoslovak Academy of Sciences, 1990.
Division:
  • Bioelectrochemistry, electroanalytical chemistry
Research Interests
  • Oxidation chemistry of biologically significant nitrogen heterocyclic compounds including chemical neurotransmitters and neurotoxins.

Research Description

Brain Chemistry; Chemistry of Neurodegenerative Illnesses

This laboratory is exploring the fundamental chemical and neurobiological mechanisms that might underlie the selective neurodegeneration that occurs in the brain in Parkinson's disease (PD), Alzheimer's disease (AD), and as a consequence of ischemia-reperfusion (I-R, or stroke), and chronic abuse of illicit psychostimulant drugs such as methamphetamine (MA) and methylenedioxymethamphetamine (MDMA, ecstasy). One intriguing feature of the neurodegeneration that occurs in PD, AD and as a result of I-R, MA and MDMA is that one or more neuronal systems that degenerate employ a biogenic amine neurotransmitter. The biogenic amines are 5-hydroxytryptamine (5-HT; serotonin), dopamine (DA), and norepinephrine (NE). Many lines of evidence suggest that reactive oxygen species such as superoxide (O2-·) and hydroxyl (HO·) radicals are involved in the pathogenesis of PD and AD. These radicals are quite definitely key participants in the neurodegeneration evoked by I-R, MA and MDMA. Thus, we are exploring the hypothesis that oxygen radical-mediated oxidation of 5-HT, DA and NE leads to the formation of endotoxic metabolites.

In particular, these unusual oxidative metabolites are believed to interfere with mitochondrial respiration and other key intraneuronal enzymes together with certain receptors by modifying critical sulfhydryl residues at their active centers. Research includes fundamental oxidation studies of 5-HT, DA and NE, particularly in the presence of cysteine and glutathione, and isolation and structural characterization of resultant putative endotoxic metabolites. The interactions of these novel compounds with intact mitochondria, mitochondrial and other enzymes and receptors are also studied.

In addition, in vivo studies with laboratory animals are employed to monitor in real-time neurochemical changes in the brain in response to certain toxic insults using microdialysis coupled to on-line HPLC with electrochemical or fluorescence detection. Furthermore, work is now underway to design therapeutic strategies to interrupt the neurodegenerative processes that occur in PD, AD, I-R and consequent to MA and MDMA abuse. These studies are all based on a thorough understanding of the brain chemistry that occurs in these disorders.

Selected Recent Publications

X-M. Shen, F. Zhang and G. Dryhurst. (1997) Oxidation of Dopamine in the Presence of Cysteine: Characterization of New Toxic Products. Chem. Res. Toxicol. 10, 147-155.

Z. Yang, M.Z. Wrona and G. Dryhurst. (1997) 5-Hydroxy-3-Ethylamino-2-Oxindole is Not Formed in Rat Brain Following a Neurotoxic Dose of Methamphetamine: Evidence that Methamphetamine Does Not Induce Hydroxyl Radical-Mediated Oxidation of Serotonin. J. Neurochem. 68, 1929-1941.

H. Li and G. Dryhurst. (1997) Irreversible Inhibition of Mitochondrial Complex I by 7(2-Aminoethyl)-3,4-Dihydro-5-Hydroxy-2H-1,4-Benzothiazine-3-Carboxylic Acid (DHBT-1): A Putative Nigral Endotoxin of Relevance to Parkinson's Disease. J. Neurochem. 69, 1530-1541.

X.-M. Shen and G. Dryhurst. (1997) Further Insights Into the Oxidation Chemistry of Norepinephrine and Epinephrine in the Presence of Cysteine. Bioorg. Chem. 25, 130-153.

G. Dryhurst. (1998) Glutathione, Cysteine and the Neuromelanin Pathway: Potential Roles in the Pathogenesis of Parkinson's Disease - A New Hypothesis. In: Glutathione in the Nervous System, C.A. Shaw, Ed., Taylor and Francis, Washington, D.C., pp. 305-342.

G. Dryhurst. (1998) Putative Endogenous Neurotoxins Derived From the Biogenic Amine Neurotransmitters. In: Pharmacology of Endogenous Neurotoxins, A. Moser, Ed., Birkhäuser, Basel. pp. 63-128.

M.Z. Wrona, and G. Dryhurst. (1998) Oxidation of serotonin by superoxide radical implications to neurodegenerative brain disorders. Chem. Res. Toxicol. 11, 639-650.

X.-M. Shen and G. Dryhurst. (1998) Iron- and manganese-catalyzed autoxidation of dopamine in the presence of L-cysteine: possible insights into iron and manganese dopaminergic neurotoxicity. Chem. Res. Toxicol. 11, 824-837.

H. Li, X.-M. Shen, and G. Dryhurst. (1998) Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1) to intermediates that irreversibly inhibit complex I and scavenges glutathione: potential relevance to the pathogenesis of Parkinson's disease. J. Neurochem. 71, 2049-2062.

 

 

University of Oklahoma Department of Chemistry and Biochemistry     620 Parrington Oval, Rm 208     Norman, OK 73019-3051