Inhibition of the functional expression of N-methyl-D-aspartate receptors in a stably transformed cell line by cyclosporin A

Biochemical Pharmacology
Ralf D SteinmetzDieter Steinhilber

Abstract

The L(tk-) cell line L12-G10 stably transformed with the human N-methyl-D-aspartate (NMDA) receptor subunits NR1-1a/NR2A showed a Ca(2+)-dependent increase in cell death, loss of mitochondrial membrane potential, and ATP depletion after agonist stimulation. Treatment of the cells with cyclosporine A (CsA) for 4h reduced glutamate-induced cell death by 60% (IC(50) of 7.1microM). The immunophilin binding drug FK506 was not effective. Short preincubation with CsA for 10 min already decreased the glutamate-induced loss of mitochondrial membrane potential while the NMDA receptor function is not affected. However, pretreatment of the cells with CsA (30 microM) for 6h reduced membrane associated NR1-1a protein amount by approximately 85%, whereas mRNA expression remained unaffected. These results suggest, that the cytoprotective effect of CsA in L12-G10 cells is due to the inhibition of the permeability transition pore on the one hand and to the inhibition of the expression of functional NMDA receptors by an additional posttranscriptional mechanism on the other hand.

References

Jan 2, 1992·Nature·M J Gething, J Sambrook
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·E R PriceC T Walsh
Aug 24, 1990·Cell·R D Klausner, R Sitia
Jan 1, 1989·Annual Review of Cell Biology·S M Hurtley, A Helenius
Jan 1, 1988·Annual Review of Cell Biology·J K Rose, R W Doms
Nov 2, 1984·Science·R E HandschumacherD W Speicher
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T M DawsonS H Snyder
Sep 1, 1996·Clinical Immunology and Immunopathology·S HoG R Crabtree
Apr 29, 1998·Reviews of Physiology, Biochemistry and Pharmacology·M Leist, P Nicotera
Dec 19, 1998·Journal of Medicinal Chemistry·G S Hamilton, J P Steiner
Feb 9, 1999·Results and Problems in Cell Differentiation·M Leist, P Nicotera
Apr 10, 1999·Nature Neuroscience·A K StoutI J Reynolds
Jan 13, 2000·International Journal of Experimental Pathology·L AndreevaC J Green
Sep 12, 2000·European Journal of Pharmacology·F RuizJ Satrústegui
Nov 30, 2000·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·W Y Almawi, O K Melemedjian
Dec 14, 2001·Journal of Neuroscience Methods·Ralf D SteinmetzDieter Steinhilber
Dec 1, 1993·Journal of Fluorescence·B Ehrenberg, L M Loew

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Citations

Dec 27, 2011·Neurochemistry International·Maiken HedegaardStephen F Traynelis

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