Identification of Rat Liver Glucose-3-phosphatase as an Inositol Monophosphatase Inhibited by Lithium

Canales, José; Buitrago, Francisco; Faraldo, Angeles; Авалос, M.; Cameselle, José Carlos

doi:10.1006/abbi.1997.0130

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…Inositol monophosphatase (IMPA) has two subtypes, IMPA1 and IMPA2, which catalyze the hydrolysis of inositol monophosphate (IP1) into free inositol, which is required for the phosphoinositol signaling pathway [5]. Lithium, an effective therapy for manic depression, has been shown to inhibit IMPase activity at clinically relevant concentrations [6,7]. A recent report demonstrated that lithium directly inhibits the enzyme activity of IMPA1, not IMPA2, in the cell-based assays [8].…”

Section: Introductionmentioning

confidence: 99%

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

Kuei

Lin

Lee

et al. 2020

JCM

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Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.

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Section: Introductionmentioning

confidence: 99%

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

Kuei

Lin

Lee

et al. 2020

JCM

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“…Various interrelated hypotheses have been formulated to clarify the pharmacological action of Li + . It has been reported that this ion inhibits several cellular enzymes, most of them involved in signal transduction pathways, such as glycogen synthase kinase-3h [3 -8], inositol monophosphatase [9][10][11][12][13][14] and adenylate cyclase [15 -17]. To explain this inhibitory effect, it has been proposed that Li + competes with Mg 2 + (a very well-known protein cofactor) for Mg 2 + binding sites in several biomolecules [7,18 -21], due to its similar chemical properties (Li + and Mg 2 + ions have similar ionic radii and ionic potentials).…”

Section: Introductionmentioning

confidence: 99%

Effects of Li+ transport and intracellular binding on Li+/Mg2+ competition in bovine chromaffin cells

Fonseca

Montezinho

Nabais

et al. 2004

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Li(+) transport, intracellular immobilisation and Li(+)/Mg(2+) competition were studied in Li(+)-loaded bovine chromaffin cells. Li(+) influx rate constants, k(i), obtained by atomic absorption (AA) spectrophotometry, in control (without and with ouabain) and depolarising (without and with nitrendipine) conditions, showed that L-type voltage-sensitive Ca(2+) channels have an important role in Li(+) uptake under depolarising conditions. The Li(+) influx apparent rate constant, k(iapp), determined under control conditions by (7)Li NMR spectroscopy with the cells immobilised and perfused, was much lower than the AA-determined value for the cells in suspension. Loading of cell suspensions with 15 mmol l(-1) LiCl led, within 90 min, to a AA-measured total intracellular Li(+) concentration, [Li(+)](iT)=11.39+/-0.56 mmol (l cells)(-1), very close to the steady state value. The intracellular Li(+) T(1)/T(2) ratio of (7)Li NMR relaxation times of the Li(+)-loaded cells reflected a high degree of Li(+) immobilisation in bovine chromaffin cells, similar to neuroblastoma, but larger than for lymphoblastoma and erythrocyte cells. A 52% increase in the intracellular free Mg(2+) concentration, Delta[Mg(2+)](f)=0.27+/-0.05 mmol (l cells)(-1) was measured for chromaffin cells loaded with the Mg(2+)-specific fluorescent probe furaptra, after 90-min loading with 15 mmol l(-1) LiCl, using fluorescence spectroscopy, indicating significant displacement of Mg(2+) by Li(+) from its intracellular binding sites. Comparison with other cell types showed that the extent of intracellular Li(+)/Mg(2+) competition at the same Li(+) loading level depends on intracellular Li(+) transport and immobilisation in a cell-specific manner, being maximal for neuroblastoma cells.

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“…Known substrates include xylulose 5phosphate, erythrose 4-phosphate, ribose 5-phosphate, fructose 1-phosphate, fructose 6-phosphate, glucose 6-phosphate and fructose 1,6-bisphosphate [15]. The discovery of a galactose-3-phosphatase from rat liver that possesses lithium sensitive IMPase activity lends weight to the idea that these activities represent multiple roles for this one enzyme within the physiological systems studied [17]. These results led to the suggestion that IMPase also has a role in the regulation of carbohydrate metabolism.…”

Section: Physiological Activities Of Impasementioning

confidence: 99%

myo-Inositol Monophosphatase: A Challenging Target for Mood Stabilising Drugs

Miller¹,

Allemann²

2007

MRMC

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Identification of Rat Liver Glucose-3-phosphatase as an Inositol Monophosphatase Inhibited by Lithium

Cited by 4 publications

References 28 publications

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

Effects of Li+ transport and intracellular binding on Li+/Mg2+ competition in bovine chromaffin cells

myo-Inositol Monophosphatase: A Challenging Target for Mood Stabilising Drugs

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