Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter.
The inositol-signaling pathway is a therapeutic target for lithium in the treatment of bipolar disorder. Inositol monophosphatases (IMPases) play a key role in inositol signaling. Lithium's ability to inhibit IMPase 1 is well known, but its effect on IMPase 2 or on the transcriptional regulation of these genes has not been studied. Here, we report the identification and characterization of the minimal promoter of IMPA2 (encoding IMPase 2) in HeLa (epithelial) and SK-N-AS (neuronal) cells. IMPA2 promoter activity appears to be contributed by different elements in the 5' flanking region, suggesting that the gene is differentially regulated in neuronal and non-neuronal cells. Furthermore, IMPA2 promoter activity in both cell lines is downregulated, in a dose-dependent manner, by lithium after treatment for only 24h. This effect is also observed in vivo. Our results suggest a possible role for IMPA2 in bipolar disorder.
Seelan
Ratnam S
RS
Molecular Neuroscience and Bioinformatics Laboratories, Mental Health, Behavioral Science and Research Services, VA Medical Center (151), Louisville, KY 40206, USA.
Parthasarathy
Latha K
LK
Parthasarathy
Ranga N
RN
D018692:Antimanic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
D018692:Antimanic Agents; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D018021:Lithium Chloride