title: Decreased expression of nardilysin in SH-SY5Y cells under ethanol stress and reduced density of nardilysin-expressing neurons in brains of alcoholics.
abstract: There is evidence for a genetic link between the metalloendopeptidase nardilysin and alcohol dependence, but the functional implication of the enzyme in alcoholism is unknown. Interestingly, some of the enzyme's substrates and interaction partners are altered in neural and non-neural tissues under the influence of ethanol consumption. To learn more about putative roles of nardilysin in alcohol dependence we studied the expression of the enzyme protein in human neuroblastoma cells under chronic ethanol exposure as well as in four brain regions of alcoholics and matched controls. Cultured SH-SY5Y cells were exposed for 96 h to two different concentrations of ethanol (50 and 200 mM). Nardilysin expression was determined using Western blotting with densitometric analysis. Furthermore, we morphometrically studied the cellular expression of nardilysin in postmortem brains of eight chronic alcoholics and nine controls by counting the number of nardilysin-immunopositive neurons in left frontal limbic area, Nuc. basalis of Meynert, paraventricular and supraoptic hypothalamic nuclei and calculating numerical cell densities. Nardilysin expression was significantly reduced after 96 h of SH-SY5Y cells exposure to 200 mM ethanol. In human brains nardilysin protein was localized to multiple neurons. In heavy drinkers there was a significantly reduced density of nardilysin immunoreactive neurons in Nuc. basalis of Meynert, paraventricular, and supraoptic nuclei. The alcohol-dependent reduction of nardilysin in cell culture and nervous tissue points to an implication of the enzyme in the pathophysiology of alcoholism.
authors.affiliation: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. Electronic address: Hans-Gert.Bernstein@med.ovgu.de.
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Rolf
authors.initials: R
authors.lastname: Stricker
authors.forename: Katja
authors.initials: K
authors.lastname: Zschiebsch
authors.forename: Susan
authors.initials: S
authors.lastname: Müller
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Georg
authors.initials: G
authors.lastname: Reiser
mesh_terms: D000437:Alcoholism / Q000473:pathology* / Q000523:psychology; D001921:Brain / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D011180:Postmortem Changes
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D008666:Metalloendopeptidases; C087976:nardilysin