Chemical modulation of metallothionein I and III mRNA in mouse brain.
Metallothioneins (MTs) are sulfhydryl-rich proteins. MT-I and MT-II are found in all tissues of the body, while MT-III exists only in brain. Regulation of MT-I and MT-III mRNA was studied in brain and liver of control C57BL/6J mice and mice given chemicals known to increase MT-I, namely, lipopolysaccharide (LPS), zinc chloride (Zn), cadmium chloride (Cd), dexamethasone (Dex), ethanol, and kainic acid (KA). Northern blot analysis revealed that MT-I mRNA levels in liver were induced dramatically (12-27-fold over basal levels) by all of the chemicals, while in brain only LPS produced an increase in MT-I mRNA (2-fold). Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30%. Because brain is such a heterogenous tissue, in situ hybridization was used to localize MT-I and MT-III mRNA in control and treated mice. MT-I mRNA signal, which was most abundant in the glial cells of the Purkinje cell layer of the cerebellum in control mice, appeared to be enhanced in mice given the MT-I inducers (LPS, Zn, Cd, Dex, ethanol, and KA). MT-I mRNA hybridization signal was also enhanced in the olfactory bulbs from LPS- and Cd-treated mice, while this signal was present but weak in control brains. MT-III mRNA hybridization signals were localized in hippocampus and co-localized with MT-I message in the glial cells of the Purkinje cell layer of the cerebellum. In addition, diffuse MT-III mRNA signals were visible in areas of the cerebral cortex, and in the molecular layer of the cerebellum. Signals for MT-III in hippocampus appeared to be reduced by KA, Dex and LPS treatment, while in the cortical region, MT-III mRNA signals appeared to be enhanced by KA, Cd, and ethanol treatment. In conclusion, both MT-I and MT-III expression in brain appears to be modulated by exogenous treatment, however, the changes are small in relation to those observed in liver. Chemical-induced alterations of MT mRNA are non-uniform throughout the brain, and thus best studied in a region-specific manner.
Zheng
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Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Berman
N E
NE
Klaassen
C D
CD
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002712:Chlorides / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017967:Zinc Compounds; D002104:Cadmium; D000431:Ethanol; D003907:Dexamethasone; C016837:zinc chloride; D008668:Metallothionein; D019256:Cadmium Chloride; D007608:Kainic Acid