Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells

Ikari, Akira; Sanada, Ayumi; Sawada, Hayato; Okude, Chiaki; Tonegawa, Chie; Sugatani, Junko

doi:10.1016/j.bbamem.2010.11.006

Cited by 23 publications

(18 citation statements)

References 34 publications

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“…This study demonstrated that TRPM6 activity was increased upon binding of EGF to EGFR, making EGF the first magnesiotropic hormone. The increased activity results from an increase in the mobility and cell-surface expression of TRPM6 [52]. These findings matched perfectly with earlier observations that certain EGFR-targeting chemotherapeutic agents cause hypomagnesaemia.…”

Section: Egfr Modulatorssupporting

confidence: 90%

Drug-induced alterations in Mg2+ homoeostasis

et al. 2012

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Magnesium (Mg2+) balance is tightly regulated by the concerted actions of the intestine, bone and kidneys. This balance can be disturbed by a broad variety of drugs. Diuretics, modulators of the EGFR (epidermal growth factor receptor), proton pump inhibitors, antimicrobials, calcineurin inhibitors and cytostatics may all cause hypomagnesaemia, potentially leading to tetany, seizures and cardiac arrhythmias. Conversely, high doses of Mg2+ salts, frequently administered as an antacid or a laxative, may lead to hypermagnesaemia causing various cardiovascular and neuromuscular abnormalities. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg2+ balance will indicate ways of prevention and treatment of these adverse effects and could potentially provide more insight into Mg2+ homoeostasis.

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Section: Egfr Modulatorssupporting

confidence: 90%

Drug-induced alterations in Mg2+ homoeostasis

et al. 2012

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“…In an in vitro study using NRK-52E cells derived from normal rat renal tubules, Ikari et al revealed that sirolimus reduces mRNA expression TRPM6 at the DCT via inhibition of EGF-induced increase in TRPM6 expression, presumably by reducing the stability of TRPM6 mRNA. 63 In contrast, in a study using male Wistar rats treated with rapamycin, da Silva et al reported increased TRPM6 expression. 64 The magnesiuric effect of rapamycin in the latter study was thought to be due to the primary downregulation of NKCC2 protein expression leading to magnesiuria, followed by a secondary compensatory response with increased DCT TRPM6 protein expression.…”

Section: Reduced Tal Reabsorptionmentioning

confidence: 89%

Hypomagnesemia: a clinical perspective

Pham¹,

Pham²,

Pham³

et al. 2014

IJNRD

144

119

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Although magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.

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“…mTOR participates in this process in nonneuronal cells. For example, rapamycin decreases the steady-state level of collagen ( COL1A1 and COL1A2 ) mRNA in fibroblasts and destabilizes inducible nitric oxide synthase mRNA in astrocytes and transient receptor potential melastatin 6 in renal tubular epithelial cells [68–70]. Whether mTOR stabilizes transcripts that are induced by status epilepticus remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Kainic Acid Induces mTORC1-Dependent Expression of Elmo1 in Hippocampal Neurons

et al. 2016

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Epileptogenesis is a process triggered by initial environmental or genetic factors that result in epilepsy and may continue during disease progression. Important parts of this process include changes in transcriptome and the pathological rewiring of neuronal circuits that involves changes in neuronal morphology. Mammalian/mechanistic target of rapamycin (mTOR) is upregulated by proconvulsive drugs, e.g., kainic acid, and is needed for progression of epileptogenesis, but molecular aspects of its contribution are not fully understood. Since mTOR can modulate transcription, we tested if rapamycin, an mTOR complex 1 inhibitor, affects kainic acid-evoked transcriptome changes. Using microarray technology, we showed that rapamycin inhibits the kainic acid-induced expression of multiple functionally heterogeneous genes. We further focused on engulfment and cell motility 1 (Elmo1), which is a modulator of actin dynamics and therefore could contribute to pathological rewiring of neuronal circuits during epileptogenesis. We showed that prolonged overexpression of Elmo1 in cultured hippocampal neurons increased axonal growth, decreased dendritic spine density, and affected their shape. In conclusion, data presented herein show that increased mTORC1 activity in response to kainic acid has no global effect on gene expression. Instead, our findings suggest that mTORC1 inhibition may affect development of epilepsy, by modulating expression of specific subset of genes, including Elmo1, and point to a potential role for Elmo1 in morphological changes that accompany epileptogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-9821-6) contains supplementary material, which is available to authorized users.

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Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells

Cited by 23 publications

References 34 publications

Drug-induced alterations in Mg2+ homoeostasis

Drug-induced alterations in Mg2+ homoeostasis

Hypomagnesemia: a clinical perspective

Kainic Acid Induces mTORC1-Dependent Expression of Elmo1 in Hippocampal Neurons

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