Cisplatin-induced nephrotoxicity in vitro: increases in cytosolic calcium concentration and the inhibition of cytosolic and mitochondrial protein kinase C

Toxicology Letters
J G Zhang, W E Lindup

Abstract

Exposure of rat kidney cortical slices to cisplatin (2 mM) significantly increased the activity of cytosolic phosphorylase a, indicating that the concentration of cytosolic Ca2+ was increased. Dithiothreitol (DTT), a sulphydryl reducing agent, markedly reversed this effect but N,N'-diphenylphenylenediamine (DPPD), an antioxidant, did not. Cisplatin inhibited protein kinase C (PKC) activity in both mitochondrial and cytosolic fractions after the slices were exposed to cisplatin. Both DTT and DPPD prevented these inhibitory effects of cisplatin on PKC but diethylmaleate, a glutathione depletor, potentiated this inhibitory effect. These results suggest that the increase in cytosolic Ca2+ is related to depletion of SH-groups, but independent of lipid peroxidation, whereas inhibition of PKC may be associated with cisplatin-induced depletion of thiols and with lipid peroxidation.

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Citations

Jun 18, 2002·European Journal of Pharmacology·Antonio ZiccaMaurizio Viale
Jan 1, 2013·Acta Crystallographica. Section D, Biological Crystallography·John R Helliwell, Simon William Maurice Tanley
May 9, 2012·PloS One·Iftekhar HassanImrana Naseem
Oct 7, 2015·Archives of Toxicology·Cheng-Lung ChenLi-Heng Pao
Nov 30, 2006·Journal of Biochemistry and Molecular Biology·Heba Hosny MansourNadia Mohamed Fahmy
Jun 30, 2004·Chemico-biological Interactions·Cristina MarzanoDolores Fregona
Aug 31, 2006·Nephron. Physiology·Ivan Sabolić
Jun 7, 2019·The Journal of Biological Chemistry·Satya Narayan DeepRanjana Poddar
Sep 10, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Simon W M TanleyJohn R Helliwell
Dec 24, 1997·The Journal of Pharmacy and Pharmacology·J G Zhang, W E Lindup
Jan 23, 2020·Drug Metabolism and Pharmacokinetics·Yunpeng ZhangKazuo Matsubara

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