TVP1022 protects neonatal rat ventricular myocytes against doxorubicin-induced functional derangements.

The Journal of Pharmacology and Experimental Therapeutics
Alexandra BerdichevskiOfer Binah

Abstract

Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-epsilon and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 microM, 24 h) prevented doxorubicin (0.5 microM, 24 h)-induced elevation of diastolic [Ca(2+)](i), the slowing of [Ca(2+)](i) relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermor...Continue Reading

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Citations

Nov 9, 2011·PloS One·Yohann BernardLaurent Désaubry
Apr 21, 2010·Journal of Molecular Neuroscience : MN·Boglarka RaczBalazs Gasz
Jan 25, 2012·Pharmacology & Therapeutics·Naama Zeevi-LevinOfer Binah
Mar 21, 2012·Fundamental & Clinical Pharmacology·Sergey KharinDmitry Shmakov
Feb 18, 2011·British Journal of Pharmacology·Offir ErtrachtOfer Binah
Jan 18, 2017·Pharmacology Research & Perspectives·Assaf MalkaOfer Binah
Apr 23, 2015·Journal of Cardiovascular Pharmacology·Assaf MalkaOfer Binah
May 24, 2017·Frontiers in Pharmacology·Esperanza HerradónVisitacion López-Miranda

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