tailieunhanh - Báo cáo khoa học: High and complementary expression patterns of alcohol and aldehyde dehydrogenases in the gastrointestinal tract Implications for Parkinson’s disease

Parkinson’s disease (PD) is a heterogeneous movement disorder character-ized by progressive degeneration of dopamine neurons in substantia nigra. We have previously presented genetic evidence for the possible involvement of alcohol and aldehyde dehydrogenases (ADH; ALDH) by identifying genetic variants in ADH1C and ADH4 that associate with PD. | ễFEBS Journal High and complementary expression patterns of alcohol and aldehyde dehydrogenases in the gastrointestinal tract Implications for Parkinson s disease Marie Westerlund1 Andrea Carmine Belin1 Michael R. Felder2 Lars Olson1 and Dagmar Galter1 1 Department of Neuroscience Karolinska Institutet Stockholm Sweden 2 Department of BiologicalSciences University of South Carolina Columbia USA Keywords ADH1 ADH4 ALDH1 epithelium in situ hybridization Correspondence D. Galter Department of Neuroscience Karolinska Institutet 171 77 Stockholm Sweden Tel 46 8 524 870 18 Fax 46 8 32 37 42 E-mail Website http Received 29 September 2006 revised 12 December 2006 accepted 22 December 2006 doi Parkinson s disease PD is a heterogeneous movement disorder characterized by progressive degeneration of dopamine neurons in substantia nigra. We have previously presented genetic evidence for the possible involvement of alcohol and aldehyde dehydrogenases ADH ALDH by identifying genetic variants in ADH1C and ADH4 that associate with PD. The absence of the corresponding mRNA species in the brain led us to the hypothesis that one cause of PD could be defects in the defense systems against toxic aldehydes in the gastrointestinal tract. We investigated cellular expression of Adh1 Adh3 Adh4 and Aldhl mRNA along the rodent GI tract. Using oligonucleotide in situ hybridization probes we were able to resolve the specific distribution patterns of closely related members of the ADH family. In both mice and rats Adh4 is transcribed in the epithelium of tongue esophagus and stomach whereas Adh1 was active from stomach to rectum in mice and in duodenum colon and rectum in rats. Adh1 and Adh4 mRNAs were present in the mouse gastric mucosa in nonoverlapping patterns with Adh1 in the gastric glands and Adh4 in the gastric pits. Aldh1 was found in epithelial cells from tongue to jejunum in rats and from esophagus to colon in mice. Adh3 .