PMID- 24893265 OWN - NLM STAT- MEDLINE DCOM- 20150629 LR - 20211021 IS - 1557-7716 (Electronic) IS - 1523-0864 (Print) IS - 1523-0864 (Linking) VI - 21 IP - 14 DP - 2014 Nov 10 TI - The role of SUMO-1 in cardiac oxidative stress and hypertrophy. PG - 1986-2001 LID - 10.1089/ars.2014.5983 [doi] AB - AIMS: Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac hypertrophy, the role of SUMO-1 has not been defined and our study's goals were to examine the effects of modulating SUMO-1 on the hypertrophic response both in vitro and in vivo and to examine whether oxidative stress (during cardiac hypertrophy) is abrogated by SUMO-1 gene transfer. RESULTS: In mice undergoing transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the compensated stage of hypertrophy and then dropped sharply during the transition to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the hypertrophic response in the presence of phenylephrine. Adeno-associated vector type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing hypertrophy after TAC and prevented the development of left ventricular dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure. INNOVATION AND CONCLUSION: The results of this study indicate that post-translational modifications of SERCA2a caused by the toxic environment of the hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox Signal. 21, 1986-2001. FAU - Lee, Ahyoung AU - Lee A AD - 1 Department of Cardiology, Cardiovascular Research Center , Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Jeong, Dongtak AU - Jeong D FAU - Mitsuyama, Shinichi AU - Mitsuyama S FAU - Oh, Jae Gyun AU - Oh JG FAU - Liang, Lifan AU - Liang L FAU - Ikeda, Yoshiyuki AU - Ikeda Y FAU - Sadoshima, Junichi AU - Sadoshima J FAU - Hajjar, Roger J AU - Hajjar RJ FAU - Kho, Changwon AU - Kho C LA - eng GR - R01 HL091469/HL/NHLBI NIH HHS/United States GR - HHSN268201000045C/HL/NHLBI NIH HHS/United States GR - R01 HL117505/HL/NHLBI NIH HHS/United States GR - P20HL100396/HL/NHLBI NIH HHS/United States GR - R00 HL116645/HL/NHLBI NIH HHS/United States GR - R01 HL067724/HL/NHLBI NIH HHS/United States GR - HL117505 01A1/HL/NHLBI NIH HHS/United States GR - R01 HL112330/HL/NHLBI NIH HHS/United States GR - R01 AG023039/AG/NIA NIH HHS/United States GR - R01 HL102738/HL/NHLBI NIH HHS/United States GR - HL088434/HL/NHLBI NIH HHS/United States GR - R01 HL093183/HL/NHLBI NIH HHS/United States GR - K99 HL116645/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140804 PL - United States TA - Antioxid Redox Signal JT - Antioxidants & redox signaling JID - 100888899 RN - 0 (SUMO-1 Protein) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Cardiomegaly/genetics/*metabolism/pathology MH - Cells, Cultured MH - Gene Targeting MH - Heart Failure/genetics/*metabolism/pathology MH - Mice MH - Myocardium/metabolism/pathology MH - Myocytes, Cardiac/metabolism/pathology MH - *Oxidative Stress MH - SUMO-1 Protein/*genetics/metabolism MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism PMC - PMC4208582 EDAT- 2014/06/04 06:00 MHDA- 2015/06/30 06:00 PMCR- 2014/11/10 CRDT- 2014/06/04 06:00 PHST- 2014/06/04 06:00 [entrez] PHST- 2014/06/04 06:00 [pubmed] PHST- 2015/06/30 06:00 [medline] PHST- 2014/11/10 00:00 [pmc-release] AID - 10.1089/ars.2014.5983 [pii] AID - 10.1089/ars.2014.5983 [doi] PST - ppublish SO - Antioxid Redox Signal. 2014 Nov 10;21(14):1986-2001. doi: 10.1089/ars.2014.5983. Epub 2014 Aug 4.