Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity

Archives of Toxicology
Dong ZhengTianqing Peng

Abstract

We recently reported that doxorubicin decreased the expression of calpain-1/2, while inhibition of calpain activity promoted doxorubicin-induced cardiac injury in mice. In this study, we investigated whether and how elevation of calpain-2 could affect doxorubicin-triggered cardiac injury. Transgenic mice with inducible cardiomyocyte-specific expression of calpain-2 were generated. An acute cardiotoxicity was induced in both transgenic mice and their relevant wild-type littermates by injection of a single dose of doxorubicin (20 mg/kg) and cardiac injury was analyzed 5 days after doxorubicin injection. Cardiomyocyte-specific up-regulation of calpain-2 did not induce any adverse cardiac phenotypes under physiological conditions by age 3 months, but significantly reduced myocardial injury and improved myocardial function in doxorubicin-treated mice. Cardiac protection of calpain-2 up-regulation was also observed in a mouse model of chronic doxorubicin cardiotoxicity. Up-regulation of calpain-2 increased the protein levels of mitogen activated protein kinase phosphatase-1 (MKP-1) in cultured mouse cardiomyocytes and heart tissues. Over-expression of MKP-1 prevented, whereas knockdown of MKP-1 augmented doxorubicin-induced apoptosis...Continue Reading

References

Mar 10, 2001·Experimental Cell Research·L Simpson, R Parsons
Oct 24, 2002·Journal of Molecular and Cellular Cardiology·Yoshiaki Taniyama, Kenneth Walsh
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Dec 13, 2003·Circulation Research·Peter H Sugden
Mar 18, 2005·American Journal of Physiology. Heart and Circulatory Physiology·H LouP K Singal
Feb 24, 2007·Nature Reviews. Immunology·Yusen LiuLeif D Nelin
Mar 3, 2007·Progress in Cardiovascular Diseases·Genzou Takemura, Hisayoshi Fujiwara
Apr 5, 2008·Journal of the American College of Cardiology·Karin PrzyklenkPeter Whittaker
Aug 30, 2008·Cell Cycle·Yuki Kuwano, Myriam Gorospe
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Federico RojoJoan Albanell
Mar 17, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Tadashi YoshidaPatrice Delafontaine
Aug 14, 2010·Free Radical Biology & Medicine·Rajarajan A ThandavarayanYoshifusa Aizawa
Jul 29, 2011·The Journal of Biological Chemistry·Manabu TaneikeKinya Otsu
Mar 20, 2012·The Journal of Biological Chemistry·Wai-chi HoPeter A Greer
Apr 25, 2012·Basic Research in Cardiology·Yongwei YaoTao Rui
Mar 5, 2013·Cardiovascular Research·Yanpeng WangTianqing Peng
Mar 8, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Victor BrizMichel Baudry
Nov 8, 2014·The Journal of Pharmacology and Experimental Therapeutics·Ying-Yu ZhangZhao Zhang
Apr 22, 2016·American Journal of Physiology. Cell Physiology·Prasanna AbeyrathnaYunchao Su
May 30, 2017·Cardiovascular Drugs and Therapy·Ingrid WebsterBarbara Huisamen

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Methods Mentioned

BETA
zymography
transgenic
ubiquitination
ELISA

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