Mahesh P. Gupta
Title | Professor |
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Institution | University of Chicago |
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Department | Surgery-Cardiac |
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Address | Chicago IL 60637
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Overview Primary focus of my lab is to understand the molecular basis of heart failure, particularly, the role played by the chromatin remodeling enzymes in muscle gene regulation, cellular senescence and cardiac hypertrophy and fibrosis. Heart failure is a pathological state in which the heart is unable to pump blood at a rate commensurate with requirements of the metabolizing tissues. It is usually caused by a defect in myocardial contraction. Reduced myocardial contractile function may reflect a decrease in number of viable myocytes, dysfunction of viable myocytes, or alterations to the intrinsic contractile activity of individual myocytes. At the molecular level, several abnormalities have been observed, including alterations in the expression of numerous genes that are central to the normal structure and function of the heart; however, the basic mechanism of heart failure is not yet fully understood. With recent advancements in cell biology, it has become clear that factors modifying chromatin structure, e.g. histone deacetylases, acetyltransferases and sirtuins play a fundamental role in this process. In addition to modifying chromatin structure, these enzymes also play a role out side the nucleus. We are trying to understand how these enzymes modify mitochondrial proteins and regulate the cell-survivability and contractile function, in response to various pathophysiological stresses, including obesity/diabetes, hemodynamic overloads and aging.
Biography All India Institute of Medical Sciences, New Delhi | MS and PhD | 1985 | Physiology and Pharmacology | University of Chicago, Chicago | Post-doctoral training (mentor Dr. Radovan Zak) | | Cardiac cell biology |
1989 - 1991 | Senior Reserach Fellowship , American Heart Association | 2016 | Member of the Scientific Advisory Board , International Academy of Cardiology | 2016 | Distinguished Fuculty, American Society of Nepharology | 2015 | Vincenzo Panagia Distinguished lecture award, University of Manitoba | 2008 | Fellow of American Heart Association (FAHA), Basic science council of American Heart Association | 1987 | Upjohn Award for the best research paper, International Society of Heart Reserach | 1984 | Institutional Award of merit , All India institute of Medical Sciences, New Delhi | 1980 | National Merit Scholarship, Board of Education Government of India |
ORNG Applications Research R01HL068083 (GUPTA, MAHESH P)Sep 30, 2001 - Jul 31, 2005 NIH Alpha-Myosin Heavy Chain Gene Repression &Heart Failure Role: Principal Investigator |
| R01HL077788 (GUPTA, MAHESH P)Aug 1, 2004 - May 31, 2009 NIH Histone deacetylases in pathogenesis of heart failure Role: Principal Investigator |
| R01HL083423 (GUPTA, MAHESH P)Mar 15, 2007 - Feb 28, 2013 NIH The Role of PARP-SIR2 Signaling in Heart Failure Role: Principal Investigator |
| R01HL111455 (GUPTA, MAHESH P)Feb 15, 2013 - Jan 31, 2017 NIH Activation of sirtuins to prevent adverse cardiac remodeling after CABG Role: Principal Investigator |
| R01HL117041 (GUPTA, MAHESH P)Jun 1, 2013 - Apr 30, 2017 NIH Blocking cardiac toxicity of anticancer drugs Role: Principal Investigator |
| R01HL136712 (GUPTA, MAHESH P)Jul 15, 2018 - Jun 30, 2022 NIH Exploring roles of sirtuins in protecting diabetic hearts Role: Principal Investigator |
| R01HL143488 (GUPTA, MAHESH P)Sep 1, 2018 - Jul 31, 2022 NIH Improving post-surgery recovery of failing hearts by targeting cardiomyocyte senescence Role: Principal Investigator |
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Kanwal A, Pillai VB, Samant S, Gupta M, Gupta MP. The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy. FASEB J. 2019 Oct; 33(10):10872-10888. PMID: 31318577.
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Samant SA, Pillai VB, Gupta MP. Cellular mechanisms promoting cachexia and how they are opposed by sirtuins 1. Can J Physiol Pharmacol. 2019 Apr; 97(4):235-245. PMID: 30407871.
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Sarikhani M, Mishra S, Maity S, Kotyada C, Wolfgeher D, Gupta MP, Singh M, Sundaresan NR. SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation. Elife. 2018 03 05; 7. PMID: 29504933.
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Sarikhani M, Mishra S, Desingu PA, Kotyada C, Wolfgeher D, Gupta MP, Singh M, Sundaresan NR. SIRT2 regulates oxidative stress-induced cell death through deacetylation of c-Jun NH2-terminal kinase. Cell Death Differ. 2018 09; 25(9):1638-1656. PMID: 29449643.
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Samant SA, Kanwal A, Pillai VB, Bao R, Gupta MP. The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy. Sci Rep. 2017 09 19; 7(1):11877. PMID: 28928419.
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Pillai VB, Kanwal A, Fang YH, Sharp WW, Samant S, Arbiser J, Gupta MP. Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice. Oncotarget. 2017 May 23; 8(21):34082-34098. PMID: 28423723.
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Nagalingam RS, Sundaresan NR, Gupta MP, Geenen DL, Solaro RJ, Gupta M. A cardiac-enriched microRNA, miR-378, blocks cardiac hypertrophy by targeting Ras signaling. J Biol Chem. 2017 03 24; 292(12):5123. PMID: 28341711.
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Nagalingam RS, Sundaresan NR, Noor M, Gupta MP, Solaro RJ, Gupta M. Deficiency of cardiomyocyte-specific microRNA-378 contributes to the development of cardiac fibrosis involving a transforming growth factor ß (TGFß1)-dependent paracrine mechanism. J Biol Chem. 2017 03 24; 292(12):5124. PMID: 28341712.
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Nan J, Zhu W, Rahman MS, Liu M, Li D, Su S, Zhang N, Hu X, Yu H, Gupta MP, Wang J. Molecular regulation of mitochondrial dynamics in cardiac disease. Biochim Biophys Acta Mol Cell Res. 2017 Jul; 1864(7):1260-1273. PMID: 28342806.
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Bindu S, Pillai VB, Kanwal A, Samant S, Mutlu GM, Verdin E, Dulin N, Gupta MP. SIRT3 blocks myofibroblast differentiation and pulmonary fibrosis by preventing mitochondrial DNA damage. Am J Physiol Lung Cell Mol Physiol. 2017 01 01; 312(1):L68-L78. PMID: 27815257.
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Akamata K, Wei J, Bhattacharyya M, Cheresh P, Bonner MY, Arbiser JL, Raparia K, Gupta MP, Kamp DW, Varga J. SIRT3 is attenuated in systemic sclerosis skin and lungs, and its pharmacologic activation mitigates organ fibrosis. Oncotarget. 2016 Oct 25; 7(43):69321-69336. PMID: 27732568.
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Bindu S, Pillai VB, Gupta MP. Role of Sirtuins in Regulating Pathophysiology of the Heart. Trends Endocrinol Metab. 2016 08; 27(8):563-573. PMID: 27210897.
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Pillai VB, Bindu S, Sharp W, Fang YH, Kim G, Gupta M, Samant S, Gupta MP. Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin-induced cardiomyopathy in mice. Am J Physiol Heart Circ Physiol. 2016 Apr 15; 310(8):H962-72. PMID: 26873966.
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Sundaresan NR, Bindu S, Pillai VB, Samant S, Pan Y, Huang JY, Gupta M, Nagalingam RS, Wolfgeher D, Verdin E, Gupta MP. SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3ß. Mol Cell Biol. 2015 Dec 14; 36(5):678-92. PMID: 26667039.
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Tanaka A, Kawaji K, Patel AR, Tabata Y, Burke MC, Gupta MP, Ota T. In situ constructive myocardial remodeling of extracellular matrix patch enhanced with controlled growth factor release. J Thorac Cardiovasc Surg. 2015 Nov; 150(5):1280-90.e2. PMID: 26344683.
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Samant SA, Pillai VB, Sundaresan NR, Shroff SG, Gupta MP. Histone Deacetylase 3 (HDAC3)-dependent Reversible Lysine Acetylation of Cardiac Myosin Heavy Chain Isoforms Modulates Their Enzymatic and Motor Activity. J Biol Chem. 2015 Jun 19; 290(25):15559-69. PMID: 25911107.
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Pillai VB, Samant S, Sundaresan NR, Raghuraman H, Kim G, Bonner MY, Arbiser JL, Walker DI, Jones DP, Gius D, Gupta MP. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nat Commun. 2015 Apr 14; 6:6656. PMID: 25871545.
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Hu S, Liu H, Ha Y, Luo X, Motamedi M, Gupta MP, Ma JX, Tilton RG, Zhang W. Posttranslational modification of Sirt6 activity by peroxynitrite. Free Radic Biol Med. 2015 Feb; 79:176-85. PMID: 25476852.
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Ming M, Han W, Zhao B, Sundaresan NR, Deng CX, Gupta MP, He YY. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer. Cancer Res. 2014 Oct 15; 74(20):5925-33. PMID: 25320180.
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Nagalingam RS, Sundaresan NR, Noor M, Gupta MP, Solaro RJ, Gupta M. Deficiency of cardiomyocyte-specific microRNA-378 contributes to the development of cardiac fibrosis involving a transforming growth factor ß (TGFß1)-dependent paracrine mechanism. J Biol Chem. 2014 Sep 26; 289(39):27199-214. PMID: 25104350.
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Alrob OA, Sankaralingam S, Ma C, Wagg CS, Fillmore N, Jaswal JS, Sack MN, Lehner R, Gupta MP, Michelakis ED, Padwal RS, Johnstone DE, Sharma AM, Lopaschuk GD. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res. 2014 Sep 01; 103(4):485-97. PMID: 24966184.
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Pillai VB, Sundaresan NR, Gupta MP. Regulation of Akt signaling by sirtuins: its implication in cardiac hypertrophy and aging. Circ Res. 2014 Jan 17; 114(2):368-78. PMID: 24436432.
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Babitha V, Yadav VP, Chouhan VS, Hyder I, Dangi SS, Gupta M, Khan FA, Taru Sharma G, Sarkar M. Luteinizing hormone, insulin like growth factor-1, and epidermal growth factor stimulate vascular endothelial growth factor production in cultured bubaline granulosa cells. Gen Comp Endocrinol. 2014 Mar 01; 198:1-12. PMID: 24361167.
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Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, Archer SL, Chan DC, Gupta MP. SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol. 2014 Mar; 34(5):807-19. PMID: 24344202.
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Velmurugan GV, Sundaresan NR, Gupta MP, White C. Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes. Cardiovasc Res. 2013 Oct 01; 100(1):143-50. PMID: 23715558.
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Nagalingam RS, Sundaresan NR, Gupta MP, Geenen DL, Solaro RJ, Gupta M. A cardiac-enriched microRNA, miR-378, blocks cardiac hypertrophy by targeting Ras signaling. J Biol Chem. 2013 Apr 19; 288(16):11216-32. PMID: 23447532.
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Pillai VB, Sundaresan NR, Kim G, Samant S, Moreno-Vinasco L, Garcia JG, Gupta MP. Nampt secreted from cardiomyocytes promotes development of cardiac hypertrophy and adverse ventricular remodeling. Am J Physiol Heart Circ Physiol. 2013 Feb 01; 304(3):H415-26. PMID: 23203961.
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Sundaresan NR, Vasudevan P, Zhong L, Kim G, Samant S, Parekh V, Pillai VB, Ravindra PV, Gupta M, Jeevanandam V, Cunningham JM, Deng CX, Lombard DB, Mostoslavsky R, Gupta MP. The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nat Med. 2012 Nov; 18(11):1643-50. PMID: 23086477.
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Govindan S, Sarkey J, Ji X, Sundaresan NR, Gupta MP, de Tombe PP, Sadayappan S. Pathogenic properties of the N-terminal region of cardiac myosin binding protein-C in vitro. J Muscle Res Cell Motil. 2012 May; 33(1):17-30. PMID: 22527638.
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Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ, Nagalingam RS, Gupta M. A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival. J Biol Chem. 2012 Apr 13; 287(16):12913-26. PMID: 22367207.
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Zieger MA, Gupta MP, Wang M. Proteomic analysis of endothelial cold-adaptation. BMC Genomics. 2011 Dec 22; 12:630. PMID: 22192797.
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Sundaresan NR, Pillai VB, Wolfgeher D, Samant S, Vasudevan P, Parekh V, Raghuraman H, Cunningham JM, Gupta M, Gupta MP. The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci Signal. 2011 Jul 19; 4(182):ra46. PMID: 21775285.
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Pillai VB, Sundaresan NR, Samant SA, Wolfgeher D, Trivedi CM, Gupta MP. Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes. Mol Cell Biol. 2011 Jun; 31(11):2349-63. PMID: 21444723.
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Sundaresan NR, Pillai VB, Gupta MP. Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy. J Mol Cell Cardiol. 2011 Oct; 51(4):614-8. PMID: 21276800.
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Samant SA, Courson DS, Sundaresan NR, Pillai VB, Tan M, Zhao Y, Shroff SG, Rock RS, Gupta MP. HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity. J Biol Chem. 2011 Feb 18; 286(7):5567-77. PMID: 21177250.
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McConville JF, Fernandes DJ, Churchill J, Dewundara S, Kogut P, Shah S, Fuchs G, Kedainis D, Bellam SK, Patel NM, McCauley J, Dulin NO, Gupta MP, Adam S, Yoneda Y, Camoretti-Mercado B, Solway J. Nuclear import of serum response factor in airway smooth muscle. Am J Respir Cell Mol Biol. 2011 Sep; 45(3):453-8. PMID: 21131446.
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Pillai VB, Sundaresan NR, Jeevanandam V, Gupta MP. Mitochondrial SIRT3 and heart disease. Cardiovasc Res. 2010 Nov 01; 88(2):250-6. PMID: 20685942.
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Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, Gupta MP. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem. 2010 Jan 29; 285(5):3133-44. PMID: 19940131.
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Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest. 2009 Sep; 119(9):2758-71. PMID: 19652361.
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Rajamohan SB, Pillai VB, Gupta M, Sundaresan NR, Birukov KG, Samant S, Hottiger MO, Gupta MP. SIRT1 promotes cell survival under stress by deacetylation-dependent deactivation of poly(ADP-ribose) polymerase 1. Mol Cell Biol. 2009 Aug; 29(15):4116-29. PMID: 19470756.
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Zieger MA, Gupta MP. Hypothermic preconditioning of endothelial cells attenuates cold-induced injury by a ferritin-dependent process. Free Radic Biol Med. 2009 Mar 01; 46(5):680-91. PMID: 19135523.
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Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, Gupta MP. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol. 2008 Oct; 28(20):6384-401. PMID: 18710944.
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Gupta MP, Samant SA, Smith SH, Shroff SG. HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity. J Biol Chem. 2008 Apr 11; 283(15):10135-46. PMID: 18250163.
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Pillai JB, Chen M, Rajamohan SB, Samant S, Pillai VB, Gupta M, Gupta MP. Activation of SIRT1, a class III histone deacetylase, contributes to fructose feeding-mediated induction of the alpha-myosin heavy chain expression. Am J Physiol Heart Circ Physiol. 2008 Mar; 294(3):H1388-97. PMID: 18192211.
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Gupta MP. Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. J Mol Cell Cardiol. 2007 Oct; 43(4):388-403. PMID: 17720186.
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Paroni G, Fontanini A, Cernotta N, Foti C, Gupta MP, Yang XJ, Fasino D, Brancolini C. Dephosphorylation and caspase processing generate distinct nuclear pools of histone deacetylase 4. Mol Cell Biol. 2007 Oct; 27(19):6718-32. PMID: 17636017.
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Gupta M, Sueblinvong V, Gupta MP. The single-strand DNA/RNA-binding protein, Purbeta, regulates serum response factor (SRF)-mediated cardiac muscle gene expression. Can J Physiol Pharmacol. 2007 Mar-Apr; 85(3-4):349-59. PMID: 17612644.
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Zieger MA, Gupta MP, Siddiqui RA. Endothelial cell fatty acid unsaturation mediates cold-induced oxidative stress. J Cell Biochem. 2006 Oct 15; 99(3):784-96. PMID: 16676360.
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Han YJ, Hu WY, Chernaya O, Antic N, Gu L, Gupta M, Piano M, de Lanerolle P. Increased myosin light chain kinase expression in hypertension: Regulation by serum response factor via an insertion mutation in the promoter. Mol Biol Cell. 2006 Sep; 17(9):4039-50. PMID: 16822834.
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Pillai JB, Gupta M, Rajamohan SB, Lang R, Raman J, Gupta MP. Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2006 Oct; 291(4):H1545-53. PMID: 16632544.
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Zieger MA, Gupta MP. Endothelial cell preservation at 10 degrees C minimizes catalytic iron, oxidative stress, and cold-induced injury. Cell Transplant. 2006; 15(6):499-510. PMID: 17121161.
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Pillai JB, Isbatan A, Imai S, Gupta MP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem. 2005 Dec 30; 280(52):43121-30. PMID: 16207712.
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Sopontammarak S, Aliharoob A, Ocampo C, Arcilla RA, Gupta MP, Gupta M. Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy. Cell Biochem Biophys. 2005; 43(1):61-76. PMID: 16043884.
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Davis FJ, Pillai JB, Gupta M, Gupta MP. Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of alpha-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility. Am J Physiol Heart Circ Physiol. 2005 Mar; 288(3):H1477-90. PMID: 15388503.
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Pillai JB, Russell HM, Raman J, Jeevanandam V, Gupta MP. Increased expression of poly(ADP-ribose) polymerase-1 contributes to caspase-independent myocyte cell death during heart failure. Am J Physiol Heart Circ Physiol. 2005 Feb; 288(2):H486-96. PMID: 15374823.
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Gupta M, Sueblinvong V, Raman J, Jeevanandam V, Gupta MP. Single-stranded DNA-binding proteins PURalpha and PURbeta bind to a purine-rich negative regulatory element of the alpha-myosin heavy chain gene and control transcriptional and translational regulation of the gene expression. Implications in the repression of alpha-myosin heavy chain during heart failure. J Biol Chem. 2003 Nov 07; 278(45):44935-48. PMID: 12933792.
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Davis FJ, Gupta M, Camoretti-Mercado B, Schwartz RJ, Gupta MP. Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy. J Biol Chem. 2003 May 30; 278(22):20047-58. PMID: 12663674.
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Maeda T, Gupta MP, Stewart AF. TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters. Biochem Biophys Res Commun. 2002 Jun 21; 294(4):791-7. PMID: 12061776.
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Davis FJ, Gupta M, Pogwizd SM, Bacha E, Jeevanandam V, Gupta MP. Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts. Am J Physiol Heart Circ Physiol. 2002 Apr; 282(4):H1521-33. PMID: 11893590.
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Gupta M, Kogut P, Davis FJ, Belaguli NS, Schwartz RJ, Gupta MP. Physical interaction between the MADS box of serum response factor and the TEA/ATTS DNA-binding domain of transcription enhancer factor-1. J Biol Chem. 2001 Mar 30; 276(13):10413-22. PMID: 11136726.
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Gupta MP, Kogut P, Gupta M. Protein kinase-A dependent phosphorylation of transcription enhancer factor-1 represses its DNA-binding activity but enhances its gene activation ability. Nucleic Acids Res. 2000 Aug 15; 28(16):3168-77. PMID: 10931933.
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2000 | 1 | 2001 | 1 | 2002 | 2 | 2003 | 2 | 2004 | 2 | 2005 | 2 | 2006 | 4 | 2007 | 3 | 2008 | 4 | 2009 | 3 | 2010 | 3 | 2011 | 4 | 2012 | 4 | 2013 | 4 | 2014 | 5 | 2015 | 4 | 2016 | 4 | 2017 | 5 | 2018 | 2 | 2019 | 2 |
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