Immunosuppressants inhibit hormone-stimulated Mg2+ uptake in mouse distal convoluted tubule cells

Kim, Shang-Jin; Kang, Hyung-Sub; Jeong, Chang-Woo; Park, Sang-Yeol; Kim, In-Shik; Kim, Namsoo; Kim, Sung-Zoo; Kwak, Yong-Geun; Kim, Jin-Shang; Quamme, Gary A.

doi:10.1016/j.bbrc.2006.01.024

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…Kim et al examined the mechanisms underlying ciclosporin and FK506-induced hypomagnesemia. In this study, these medications inhibited PTH-dependent stimulation of Mg 2+ uptake in mDCT cells, by inhibiting the ERK1,2 signalling pathway [69].…”

Section: The Role Of Erk12 Signalling Along the Distal Convolute mentioning

confidence: 99%

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

Capolongo

Suzumoto

D’Acierno

et al. 2019

IJMS

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Mitogen-activated protein kinases (MAPKs) are intracellular molecules regulating a wide range of cellular functions, including proliferation, differentiation, apoptosis, cytoskeleton remodeling and cytokine production. MAPK activity has been shown in normal kidney, and its over-activation has been demonstrated in several renal diseases. The extracellular signal-regulated protein kinases (ERK 1,2) signalling pathway is the first described MAPK signaling. Intensive investigations have demonstrated that it participates in the regulation of ureteric bud branching, a fundamental process in establishing final nephron number; in addition, it is also involved in the differentiation of the nephrogenic mesenchyme, indicating a key role in mammalian kidney embryonic development. In the present manuscript, we show that ERK1,2 signalling mediates several cellular functions also in mature kidney, describing its role along the nephron and demonstrating whether it contributes to the regulation of ion channels and transporters implicated in acid-base and electrolytes homeostasis.

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Section: The Role Of Erk12 Signalling Along the Distal Convolute mentioning

confidence: 99%

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

Capolongo

Suzumoto

D’Acierno

et al. 2019

IJMS

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“…The minimum (Rmin) and maximum (Rmax) ratios were determined using 20 µM digitonin. The Rmax for Mag-fura-2 was determined by the addition of 50 mM MgCl 2 , and the Rmin was obtained by removal of the Mg 2+ and the addition of 100 mM EDTA (26). The change in [Mg 2+ ] i with time (d([Mg 2+ ] i )/dt) was determined by linear regression analysis of the fluorescence ratio over the initial 600 s and expressed in nmol/s.…”

Section: Measurement Of Intracellular Free [Mg 2+ ] I Bymentioning

confidence: 99%

Differential Effects of Cyclosporin A and Tacrolimus on Magnesium Influx in Caco2 Cells

2012

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PURPOSE: Hypomagnesemia with urinary magnesium (Mg) wasting is a well acknowledged side effect of cyclosporin A (CsA) and tacrolimus (FK506) treatments. TRPM6, TRPM7 and MagT1 are involved in the active transcellular Mg transport processes in intestine and kidney. Since Mg homeostasis is tightly controlled by the dynamic action of intestinal absorption of dietary Mg and renal excretion of Mg, we investigated whether CsA and FK506 in commercially available solutions for clinical use decrease the expression and the function of TRPM6, TRPM7 or MagT1 in the intestinal epithelial cell line Caco2. METHODS: Changes of intracellular free Mg concentrations were measured by Mag-fura-2 imaging in Mg-free medium after the addition of 1 mM MgCl2. TRPM6, TRPM7 and MagT1 were evidenced in cells by immunofluorescence. Proteins and mRNAs were quantified after 18 hours of treatment with CsA or FK506 by western-blot and real-time RT-PCR analyses, respectively. RESULTS: TRPM6 and MagT1 were evidenced on all cell membranes, TRPM7 only on the inner membranes. CsA was responsible for a profound decrease in Mg2+ influx in intestinal epithelial cells, which may result in a decrease of intestinal Mg absorption, whereas FK506 was responsible for a marked increase in Mg2+ influx. Neither CsA nor FK506 altered TRPM6, TRPM7 or MagT1 mRNA levels or MagT1 protein level. CONCLUSIONS: In Caco2 cells, Mg2+ influx was inhibited by CsA solutions whereas enhanced by FK506 solutions, without alteration of MagT1, TRPM6 and TRPM7 expression, leading to the conclusion that CsA and FK506 have opposite effects in the functional activity of the Mg transporters herein examined. In clinical use, FK506 should be preferred for patients at risk for hypomagnesemia. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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“…CyA activated ERK in LLC-PK1 cells [12], and both ERK and p38MAPK in cortical collecting duct cells [13], whereas it activated ERK but not p38MAPK in Madin-Darby canine kidney cells [6]. CyA inhibited parathyroid hormone-induced ERK activation in mouse distal convoluted tubule cells [14]. Preconditioning of rat kidneys with CyA followed by exposure to ischemia/reperfusion increased ERK activity, but decreased p38MAPK and JNK activity [15].…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

Iwayama

Sakamoto

Nawa³

et al. 2011

Nephron Extra

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Background/Aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs) and whether it regulates cyclosporine A (CyA)-induced apoptosis in renal proximal tubular cells (RPTCs). Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence) and apoptosis (determined by Hoechst 33258 staining) was examined in HK-2 cells. Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p)-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1–6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF) activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.

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Immunosuppressants inhibit hormone-stimulated Mg2+ uptake in mouse distal convoluted tubule cells

Cited by 12 publications

References 25 publications

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

Differential Effects of Cyclosporin A and Tacrolimus on Magnesium Influx in Caco2 Cells

Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

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