Keywords:

Carbonyls, lipid peroxidation, 4-hydroxy-2-nonenal (HNE), detoxification, Alzheimer's disease, Parkinson's disease, neurotoxicology, aldehyde dehydrogenases, hippocampus, astrocytes, aldo-keto reductases, mitochondria, pesticides, neuropathology

Education/Training:

• Ph.D. Department of Pharmacology, Vanderbilt University
• Research Fellow, Department of Anatomy, University College London
• Research Fellow, Department of Pathology, Vanderbilt University

Research Interests:

Oxidative damage to lipids (lipid peroxidation) is a common, toxic hallmark of multiple diseases including Alzheimer's disease, Parkinson's disease, diabetes, and atherosclerosis. Lipid peroxidation generates multiple chemically reactive aldehydes and keto products that have many biological properties. My laboratory studies how the brain detoxifies lipid peroxidation products, in particular, trans-4-hydroxy-2-nonenal (HNE). By understanding these pathways, we can develop potential therapeutic strategies. My work involves many different techniques such as immunochemistry, chiral analysis, LC-MS, HPLC, enzyme kinetics and models such as isolated mitochondria, in vitro cell culture, whole animal, and human brain tissue.

The Carbonyl Toxicology Lab 2006-7
From left: Laura (Golden Hands) Leiphon, Ales (The Coyote) Honzatko, Tonya (Rat Queen) Murphy, Matthew (Where the *&^# is my data!) Picklo, Patrick (Got any cells to contaminate?) Nelson, Eric (This sure isn't California) Long, Alex (What neurons?) Reberg, and Jiri (The Separator) Brichac. Not shown: Nathan (yeah, the cold room works) Swenby, Brandi ( I want more work!!) Kaster, and Megan (It's a job...) Beattie

Current Funding:

• UND COBRE Pilot Grant “Oxidative Damage, DHA, and Ethanol Withdrawal”

Past Funding:

• K22 ES 369 ZES1, NIH, “Lipid Peroxidation, Toxicants, and Mitochondria”
  Role: PI
• R21 AA15145-01, NIH, "“Ethanol, HNE, and the CNS”
  Role: PI
• P20 RR17699-01, Center of Biomedical Research Excellence (COBRE), NIH, “Carbonyl Metabolism in the CNS”
  Role: Project Director
• Faculty Seed Money Research Grant, " Analysis of of Chiral trans-4-Hydroxy-2-nonenal Isomers"
  Role: PI

Recent Publications:

• Swenby NP and Picklo MJ. The conserved R166 residue of ALDH5A (succinic semialdehyde dehydrogenase) has multiple functional roles. Chemico-Biological Interactions. In press.
• Picklo MJ. Ethanol intoxication increases hepatic N-lysyl protein acetylation. Biochemical Biophysical Research Communications. In press.
• Long EK, Smoliakova I, Honzatko A, and Picklo MJ. Structural Identification of a,ß-Unsaturated Aldehydes by GC/MS is Dependent upon Ionization Method. Lipids. 2008 43(8):765-74.
• Long EK, Murphy TC, Leiphon LJ, Watt J, Morrow JD, Milne GL, Howard JRH, Picklo MJ. Trans-4-Hydroxy-2-hexenal is a neurotoxic product of docosahexaenoic (22:6; n-3) acid oxidation. J. Neurochem. 2008 105(3):714-24
• Whittsett J, Picklo MJ, Vasquez-Vivar J. 4-hydroxy-2-nonenal increases superoxide anion radical in endothelial cells via stimulated GTPcyclohydrolase-1 proteasomal degradation. Atherosclerosis, Thrombosis, and Vascular Biology. 2007 27(11):2340-7.
• Honzatko A, Brichac J, and Picklo MJ. LC-ESI-MS/MS analysis of trans-4-hydroxy-2-nonenal enantiomers and metabolites. Journal of Chromatography B. 2007 857(1):115-22.
• Brichac J, Honzatko A, Picklo MJ. Direct and indirect high-performance liquid chromatography enantioseparation of trans-4-hydroxy-2-nonenoic acid. Journal of  Chromatography A. 1149(2) 305-311.
• Brichac J, Ho KK, Honzatko A, Wang R, Lu X, Weiner H, and Picklo MJ. Enantioselective Oxidation of Trans-4-Hydroxy-2-Nonenal is ALDH Isozyme and Mg2+-Dependent. Chemical Research in Toxicology. 2007 (20) 887-895.
• Picklo MJ and Montine TJ. Mitochondrial Effects of Lipid-Derived Neurotoxins. Journal of Alzheimer’s Disease. 2007; 12(2) 185-93.
• Grimsrud P, Picklo MJ, Griffin TJ, Bernlohr D. Carbonylation of adipose proteins in obesity and insulin resistance: Identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Molecular and Cellular Proteomics. 2007 (6) 624-637..
• Brichac J, Honzatko A, Leiphon L, and Picklo MJ. Trans-4-hydroxy-2-nonenal (HNE), a biochemical tool (…as well as a toxin). Proceedings of the 13th Meeting on the Molecular Biology and Enzymology of Carbonyl Metabolism. (2007) Purdue Press. H Weiner, E. Maser, and B. Plapp eds. pages 40-43.
• Kubatova A, Honzatko A, Brichac J, Long E, Picklo MJ. Analysis of HNE metabolism in CNS models. Redox Report. 2007 (12) 16-19.
• Leiphon LJ and Picklo MJ. Inhibition of aldehyde detoxification in CNS mitochondria by fungicides. Neurotoxicology. 2007 (28) 143-149.
• Milne G, Morrow JD, Picklo MJ. Elevated oxidation of docosahexaenoic acid, 22:6 (n-3), in brain regions of rats undergoing ethanol withdrawal. Neuroscience Letters. 2006 (405) 172-174.
• Kubatova A, Murphy T, Combs C, Picklo MJ. Astrocytic biotransformation of trans-4-hydroxy-2-nonenal is dose-dependent. Chemical Research in Toxicology. 2006 (19) 844-51.
• Kubatova A, Dronen LC, Picklo MJ Sr, Hawthorne SB. Midpolarity and nonpolar wood smoke particulate matter fractions deplete glutathione in RAW 264.7 macrophages. Chem Res Toxicol. 2006 Feb;19(2):255-61.
• Struys EA, Verhoeven NM , Jansen EEW , ten Brink HJ, Gupta M, Burlingame TG , Quang LS, Maher T, Rinaldo P, Snead OC, Goodwin AK, Weerts EM, Murphy TC, Picklo MJ, Jakobs C, and Gibson KM. Metabolism of gamma-hydroxybutyrate to D-2-hydroxyglutarate in mammals: further evidence for D-2-hydroxyglutarate dehydrogenase. Metabolism: Clinical and Experimental. 2006 Mar;55(3):353-8.
• Murphy T, Arntzen R, Picklo MJ. Nitrate-based vasodilators inhibit multiple vascular aldehyde dehydrogenases. Cardiovascular Toxicology. 2005;5(3):321-32.
• Honzatko A, Brichac J, Murphy TC, Reberg A, Kubatova A, Smoliakova IP, Picklo MJ. Enantioselective metabolism of trans-4-hydroxy-2-nonenal by brain mitochondria. Free Radical Biology and Medicine. 2005 (39), 913-24.
• Kubatova A, Steckler TS, Gallagher JR, Hawthorne SB, and Picklo MJ. Toxicity of wide-range polarity fractions from wood smoke and diesel exhaust particulate obtained using subcritical water. Environmental Toxicology and Chemistry. 2004 (23) 2243-2250.
• Meyer MJ, Mosely DM, and Picklo MJ. Metabolism of 4-hydroxy-trans-2-nonenal by CNS mitochondria is dependent on age and NAD+ availability. Chemical Research in Toxicology. 2004(17) 1272-79.
• Aberle NS, Picklo MJ, Amarnath V, Ren J. Inhibition of cardiac myocyte contraction by 4-hydroxy-trans-2-nonenal. Cardiovascular Toxicology. 2004 (4) 21-28.
• Murphy T, Poppe C, Porter J, Montine TJ, and Picklo MJ. 4-Hydroxy-trans-2-nonenoic acid is a GHB receptor ligand in the cerebral cortex and hippocampus. Journal of Neurochemistry. 2004 (89) 1462-70.
• Sidell KR, Montine KS, Picklo MJ, Olson SJ, Amarnath V, Montine MJ. Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum. Journal of Neuropathology and Experimental Neurology. 2003 (62) 146-153.
• Murphy T, Amarnath V, Picklo MJ. Oxidation of 4-hydroxynonenal in rat brain slices. Chemico-Biological Interactions. 2003 (143-144) 101-105.
• Murphy T, Amarnath V, Gibson KM, and Picklo MJ. Oxidation of 4-hydroxy-2-nonenal by succinic semialdehyde dehydrogenase (ALDH5A). Journal of Neurochemistry. 2003 (2):298-305.
• Murphy T, Amarnath V, Picklo MJ. Mitochondrial oxidation of 4-hydroxy-2-nonenal in rat cerebral cortex. Journal of Neurochemistry. 2003 (84) 1313-21.
• Nguyen E, and Picklo MJ. Inhibition of succinic semialdehyde dehydrogenase by alkenal products of lipid peroxidation. Biochimica et Biophysica Acta : Molecular Basis of Disease. Biochim Biophys Acta. 2003 (1637) 107-112.
• Picklo MJ, Montine TJ, Amarnath, V, and Neely MD. Carbonyl toxicology and Alzheimer's disease. Toxicology and Applied Pharmacology 2002 (184) 187-197.