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Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase

Molecular Psychiatry, ISSN: 1359-4184, Vol: 7, Issue: 2, Page: 174-180
2002
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Article Description

Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated that the behavioral effects of epi-inositol may be due to its effects on gene expression. Yeast INO1 expression was measured in northern blots. INM1 was determined by β-galactosidase activity in a strain containing the fusion gene INM1-lacZ integrated into the genome. Epi-inositol affects regulation of expression of the INO1 gene (encoding inositol-1-P synthase), even though it cannot support growth of an inositol auxotroph (suggesting that, as in mammalian cells, it is not incorporated into phosphatidylinositol). Like myo-inositol, although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol. The observed regulatory effects of epi-inositol on expression of the most highly regulated gene in the inositol biosynthetic pathway may help to explain how this inositol isomer can exert behavioral effects without being incorporated into phosphatidylinositol.

Bibliographic Details

A. Shaldubina; R. H. Belmaker; S. Ju; D. L. Vaden; D. Ding; M. L. Greenberg

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology; Medicine; Neuroscience

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