A novel mtDNA repair fusion protein attenuates maladaptive remodeling and preserves cardiac function in heart failure

American Journal of Physiology. Heart and Circulatory Physiology
Jessica M BradleyDavid J Lefer

Abstract

Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57/BL6J mice (10-12 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1-III (4 mg/kg ip) or vehicle was administered at the time of reperfusion. Male C57/BL6J mice were subjected to TAC, and Exscien1-III (4 mg/kg i.p) or vehicle was administered daily starting at 3 wk post-TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size ( P < 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6-12 wk post-TAC ( P < 0.05). Exscien1-III reduced ( P < 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mit...Continue Reading

References

Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·R M LebovitzM M Matzuk
Nov 5, 1997·The Journal of Biological Chemistry·D L Croteau, V A Bohr
Jan 30, 1999·Journal of Molecular and Cellular Cardiology·Z ChenB H Chua
Sep 16, 1999·Mutation Research·D L CroteauV A Bohr
Jun 13, 2000·Circulation Research·P M Kang, S Izumo
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·A ChoM A Reidy
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·J E KokoszkaD C Wallace
May 15, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·V GrishkoM N Gillespie
Jul 11, 2001·Journal of Molecular and Cellular Cardiology·E J LesnefskyC L Hoppel
Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·H Van RemmenA Richardson
Jun 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Allison W DobsonMark N Gillespie
Jun 6, 2003·Journal of Molecular and Cellular Cardiology·Susan H KwonWilson S Colucci
Jan 6, 2005·The Journal of Biological Chemistry·Valentina I GrishkoSusan P LeDoux
May 10, 2005·DNA Repair·Bennett Van HoutenJanine H Santos
Sep 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·John W ElrodDavid J Lefer
Nov 17, 2007·Mechanisms of Ageing and Development·Attila BacsiIstvan Boldogh
May 9, 2008·DNA Repair·Jenq-Lin YangMark P Mattson
May 31, 2011·Journal of the American College of Cardiology·Dao-Fu DaiPeter S Rabinovitch
Aug 30, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Jianxun WangPaul N Epstein
Sep 6, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Joshua M ChouteauMark N Gillespie
Sep 7, 2011·Biochemical and Biophysical Research Communications·Tetyana G VoloshenyukJason D Gardner
Jun 26, 2012·Biochimica Et Biophysica Acta·Susan D Cline
Sep 14, 2012·Current Hypertension Reports·Hugo E VerdejoSergio Lavandero
Dec 18, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Masahiro HashizumeJames C Parker
Jul 3, 2013·Circulation. Heart Failure·David J PolhemusJohn W Calvert
Jul 28, 2013·Journal of Applied Physiology·Jessica M BradleyJason D Gardner
May 10, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Jessica M BradleyDavid J Lefer
Feb 18, 2016·Heart Failure Reviews·A PiekH H W Silljé
Apr 20, 2016·Free Radical Biology & Medicine·Viktor M PastukhMykhaylo V Ruchko

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Citations

Jul 6, 2019·Cardiology Research and Practice·Nan-Bo LiuXiao-Kang Li
Mar 27, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Seok-Jo KimDavid W Kamp

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Methods Mentioned

BETA
transfection
ELISA
PCR
Assay

Software Mentioned

GraphPad
NIS Elements
Prism

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