Cyclophilin D knockout protects the mouse kidney against cyclosporin A-induced oxidative stress

American Journal of Physiology. Renal Physiology
Jelena KlawitterUwe Christians

Abstract

Mitochondrial dysfunction and oxidative stress have been implicated in cyclosporin A (CsA)-induced nephrotoxicity. CsA interacts with cyclophilin D (CypD), an essential component of the mitochondrial permeability transition pore and regulator of cell death processes. Controversial reports have suggested that CypD deletion may or may not protect cells against oxidative stress-induced cell death. In the present study, we treated wild-type (WT) mice and mice lacking CypD [peptidylprolyl isomerase F knockout (Ppif-/-) mice] with CsA to test the role and contribution of CypD to the widely described CsA-induced renal toxicity and oxidative stress. Our results showed an increase in the levels of several known uremic toxins as well as the oxidative stress markers PGF2α and 8-isoprostane in CsA-treated WT animals but not in Ppif-/- animals. Similarly, a decline in S-adenosylmethionine and the resulting methylation potential indicative of DNA hypomethylation were observed only in CsA-treated WT mice. This confirms previous reports of the protective effects of CypD deletion on the mouse kidney mediated through a stronger resistance of these animals to oxidative stress and DNA methylation damage. However, a negative effect of CsA on the gl...Continue Reading

References

Dec 10, 2019·The Journal of Toxicological Sciences·Koichi ArakawaKousei Ito
Dec 24, 2019·Expert Opinion on Investigational Drugs·Daren R UreRobert T Foster

Citations

Jun 1, 1992·European Journal of Clinical Chemistry and Clinical Biochemistry : Journal of the Forum of European Clinical Chemistry Societies·M TakedaH Endou
Dec 1, 1991·Journal of Molecular and Cellular Cardiology·W NazarethM Crompton
Aug 3, 1989·The New England Journal of Medicine·H Y LinI H Fox
May 23, 2002·Transplantation·Gary LevyConsensus on Neoral C(2): Expert Review in Transplantation (CONCERT) Group
Aug 23, 2002·Seminars in Cancer Biology·Andrew P FeinbergRolf Ohlsson
Jul 23, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Herwig-Ulf Meier-KriescheBruce Kaplan
Oct 29, 2004·The American Journal of Pathology·Jennifer L GoochJeffrey L Barnes
Nov 3, 2004·Transplantation Proceedings·Y WataraiT Koyanagi
Jan 12, 2005·Circulation·Laurent ArgaudMichel Ovize
Mar 29, 2005·The Journal of Biological Chemistry·Emy BassoPaolo Bernardi
Aug 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Anna C SchinzelStanley J Korsmeyer
Aug 8, 2006·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·David O TaylorInternational Society for Heart and Lung Transplantation
Jan 9, 2008·The Journal of Thoracic and Cardiovascular Surgery·Norihiko OkaChristopher A Caldarone
Dec 23, 2008·Chemical Research in Toxicology·Jost KlawitterVolker Schmitz
Jun 26, 2009·American Journal of Physiology. Renal Physiology·Kishor Devalaraja-NarashimhaBabu J Padanilam
Aug 19, 2009·Free Radical Biology & Medicine·Philipp J KahleThomas Gasser
Jul 1, 2005·Future Cardiology·J-M MeierJ-J Goy
Jul 24, 2010·Annals of the New York Academy of Sciences·Tsung-I Peng, Mei-Jie Jou
Mar 29, 2011·Transplantation Proceedings·E KalantarB Einollahi
Apr 15, 2011·American Journal of Physiology. Renal Physiology·Jeong Soon ParkJoel M Weinberg
May 17, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Felix SeibertTimm H Westhoff
Oct 13, 2012·Journal of Proteome Research·Jelena KlawitterUwe Christians
Jan 9, 2013·American Journal of Nephrology·Zheng XiaoYouping Li
Mar 30, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·John W Elrod, Jeffery D Molkentin
Jul 23, 2014·Journal of Hepatology·Nikolai V Naoumov

Related Concepts

Study
Biochemical Pathway
PPIF
Nephrotoxicity
Classification
Energy Transfer
Toxin
Cyclosporine
Gene Deletion
Mitochondria

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