Cellular consequences of inositol depletion.
نویسندگان
چکیده
The inositol-depletion hypothesis was suggested to explain the therapeutic mechanism of mood-stabilizing drugs. Focus was previously on the phosphatidylinositol signalling pathway and on the regulatory roles of Ins(3,4,5)P(3) and DAG (diacylglycerol). Recent findings indicate that inositol and inositol-containing molecules, including phosphoinositides and inositol phosphates, have signalling and regulatory roles in many cellular processes. This suggests that depleting inositol may lead to perturbation of a wide range of cellular functions, at least some of which may be associated with bipolar disorder.
منابع مشابه
IP3 accumulation and/or inositol depletion: two downstream lithium's effects that may mediate its behavioral and cellular changes
Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate-the consequences of lithium's inhibition of inositol monophosphatase at therapeutically relevant concentrations (the 'inositol depletion' hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol d...
متن کاملPtdIns(3,4,5)P(3) and inositol depletion as a cellular target of mood stabilizers.
Lithium (Li(+)) is the mood stabilizer most frequently used in the treatment of bipolar mood disorder; however, its therapeutic mechanism is unknown. In the 1980s, Berridge and colleagues proposed that Li(+) treatment acts via inhibition of IMPase (inositol monophosphatase) to deplete the cellular concentration of myo-inositol. Inositol depletion is also seen with the alternative mood stabilize...
متن کاملThe Inositol-3-Phosphate Synthase Biosynthetic Enzyme Has Distinct Catalytic and Metabolic Roles
Inositol levels, maintained by the biosynthetic enzyme inositol-3-phosphate synthase (Ino1), are altered in a range of disorders, including bipolar disorder and Alzheimer's disease. To date, most inositol studies have focused on the molecular and cellular effects of inositol depletion without considering Ino1 levels. Here we employ a simple eukaryote, Dictyostelium discoideum, to demonstrate di...
متن کاملEvidence against a direct role for inositol phosphate metabolism in the circadian oscillator and the blue-light signal transduction pathway in Neurospora crassa.
The inositol-depletion hypothesis proposes that the effects of Li+ on cellular functions are the result of inhibition by Li+ of the inositol monophosphate phosphatase and subsequent depletion of inositol lipids. This mechanism has been proposed to account for the effects of Li+ on the period of the circadian oscillator. Inositol phosphate metabolism has also been proposed as part of the blue-li...
متن کاملRegulation of Gene Expression by Lithium and Depletion of Inositol in Slices of Adult Rat Cortex
Lithium inhibits inositol monophosphatase at therapeutically effective concentrations, and it has been hypothesized that depletion of brain inositol levels is an important chemical alteration for lithium's therapeutic efficacy in bipolar disorder. We have employed adult rat cortical slices as a model to investigate the gene regulatory consequences of inositol depletion effected by lithium using...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Biochemical Society transactions
دوره 37 Pt 5 شماره
صفحات -
تاریخ انتشار 2009