Abstract
The balance between endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) and reactive oxygen species (ROS) production determines endothelial-mediated vascular homeostasis. Activation of protein kinase C (PKC) has been linked to imbalance of the eNOS/ROS system, which leads to endothelial dysfunction. We previously found that selective inhibition of delta PKC (deltaPKC) or selective activation of epsilon PKC (varepsilonPKC) reduces oxidative damage in the heart following myocardial infarction. In this study we determined the effect of these PKC isozymes in the survival of coronary endothelial cells (CVEC). We demonstrate here that serum deprivation of CVEC increased eNOS-mediated ROS levels, activated caspase-3, reduced Akt phosphorylation and cell number. Treatment with either the deltaPKC inhibitor, deltaV1-1, or the varepsilonPKC activator, psivarepsilonRACK, inhibited these effects, restoring cell survival through inhibition of eNOS activity. The decrease in eNOS activity coincided with specific de-phosphorylation of eNOS at Ser1179, and eNOS phosphorylation at Thr497 and Ser116. Furthermore, deltaV1-1 or psivarepsilonRACK induced physical association of eNOS with caveolin-1, an additional marker of eNOS inhibi...Continue Reading
References
Nov 1, 1992·Chemical Research in Toxicology·W H KoppenolJ S Beckman
Feb 17, 1983·Nature·A S Kraft, W B Anderson
Apr 14, 1995·Science·D Mochly-Rosen
Jun 1, 1997·Circulation Research·M ZicheM Presta
Oct 27, 1998·Nature Biotechnology·M C Souroujon, D Mochly-Rosen
Jul 11, 2002·The Journal of Biological Chemistry·Ming-Hui ZouRichard A Cohen
Jul 16, 2003·Circulation·Koichi InagakiDaria Mochly-Rosen
Apr 16, 2004·Heart·K K Griendling
Jan 18, 2006·Cell Death and Differentiation·S DonniniM Ziche
Apr 26, 2006·Cardiovascular Research·Koichi InagakiDaria Mochly-Rosen
Jul 15, 2006·Journal of Molecular and Cellular Cardiology·Peter F MountDavid A Power
Jul 27, 2006·The Journal of Pharmacology and Experimental Therapeutics·Sandra DonniniLucia Morbidelli
Nov 30, 2006·Biological Chemistry·Ulrich Förstermann
May 1, 2007·Cardiovascular Research·David M Dudzinski, Thomas Michel
May 14, 2008·FEBS Letters·Marjolaine RocheEmmanuel Bourdon
Nov 26, 2008·Free Radical Biology & Medicine·Jacek ZielonkaB Kalyanaraman
Citations
Sep 14, 2011·Oxidative Medicine and Cellular Longevity·Igor Afanas'ev
Jan 23, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hung Wen LinMiguel A Perez-Pinzon
Apr 26, 2011·Biochemical Pharmacology·Tao-Hua LanHong-Mei Tan
Aug 2, 2012·The Biochemical Journal·Odile DumontJustin C Mason
Apr 18, 2015·Cardiovascular Research·Hayley MylroieJustin C Mason
Jan 21, 2014·Biochemical Pharmacology·Hueng-Chuen FanJenn-Haung Lai
Aug 16, 2016·Vascular Pharmacology·Justin C Mason
Feb 15, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ester PaganoAngelo A Izzo
May 23, 2015·Circulation Research·Opher S KornfeldDaria Mochly-Rosen
Sep 17, 2010·Journal of Receptor and Signal Transduction Research·Vasily A Yakovlev, Ross B Mikkelsen
Mar 2, 2019·Current Neuropharmacology·Naveen SharmaHyoung-Chun Kim
Sep 17, 2015·PloS One·M Elisa Lopes-PiresSisi Marcondes
Sep 23, 2014·The Journal of Pharmacology and Experimental Therapeutics·Martina MontiLucia Morbidelli
Aug 21, 2010·Journal of Leukocyte Biology·Laurie E KilpatrickClifford S Deutschman
Nov 3, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nektarios BarabutisJohn D Catravas
Aug 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sujeong JangHeonyong Park
Sep 24, 2020·Journal of Molecular Neuroscience : MN·Claudia SticozziFederica Pessina
May 18, 2018·Oxidative Medicine and Cellular Longevity·Grazia TammaGiuseppe Calamita
Jan 18, 2020·Biomedicines·Ginevra NannelliLucia Morbidelli
Feb 4, 2011·American Journal of Physiology. Renal Physiology·Grazyna NowakAllen M Samarel
Jan 30, 2015·British Journal of Pharmacology·E TerzuoliL Morbidelli
Dec 31, 2016·PloS One·Federica FinettiLucia Morbidelli
Jan 1, 2017·Cellular and Molecular Life Sciences : CMLS·Nhat-Tu LeJun-Ichi Abe
Aug 1, 2012·Journal of Biomedical Materials Research. Part a·Amelia CataldiViviana di Giacomo
May 31, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Yixuan ZhangAn L Moens
Mar 15, 2016·Cardio-Oncology·Lucia MorbidelliMarina Ziche
Mar 2, 2021·Frontiers in Molecular Biosciences·Xiangxue LuShixiang Wang
Feb 17, 2018·Biochemical Pharmacology·Zhongwei Liu, Raouf A Khalil
Dec 18, 2015·Physiological Research·L GriecsováT Ravingerová