Potentiation of astroglial nitric oxide synthase type-2 expression by lithium chloride.
The mechanisms underlying the antimanic effects of lithium are largely unknown but may involve long-term changes in brain gene expression. To determine if lithium could modify gene expression in astrocytes, the predominant cell type in brain, we tested the effects of LiCl on expression of nitric oxide synthase type 2 (NOS-2) in cultured glial cells. Incubation of primary rat astrocytes with endotoxin [lipopolysaccharide (LPS)] and proinflammatory cytokines induced NOS-2 gene and protein expression, as assessed by nitrite production and measurement of L-citrulline synthesis in whole cell lysates. Incubation with LiCl, but not KCl, increased NOS-2 activity up to 1.6-fold. LiCl also potentiated (up to 2.7-fold) the induction of NOS-2 expression by LPS plus interferon-gamma in C6 glioma cells but had little effect on LPS-induced nitrite accumulation from mouse RAW 264.7 macrophages. LiCl increased NOS-2 mRNA steady-state levels, suggesting an effect on mRNA stability and/or NOS-2 gene transcription. These results demonstrate that LiCl can modify astroglial gene expression and suggest that chronic treatment with lithium could exacerbate inflammatory responses in brain glial cells.
Feinstein
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DL
NeuroAnesthesia Research, University of Illinois at Chicago 60607, USA.
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000201:enzymology*; D002540:Cerebral Cortex / Q000166:cytology; D002956:Citrulline / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005910:Glioma; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D018692:Antimanic Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002956:Citrulline; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D018021:Lithium Chloride