title: Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and apoptosis by improving oxidative balance.
abstract: Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct molecular mechanism underlying the oxidative stress-mediated damages to cardiomyocytes remains unknown. Curcumin (diferuloylmethane) is known for anti-hypertrophic effects, but low bioavailability makes it unsuitable to exploit its pharmacological properties. We assessed the efficacy of nanotized curcumin, i.e. nanocurcumin, in ameliorating hypoxia-induced hypertrophy and apoptosis in H9c2 cardiomyoblasts and compared it to curcumin. H9c2 cardiomyoblasts were challenged with 0.5 % oxygen, for 24 h to assess hypoxia-induced oxidative damage, hypertrophy and consequent apoptosis. The molecular mechanism underlying the protective efficacy of nanocurcumin was evaluated in regulating Raf-1/Erk-1/2 apoptosis by caspase-3/-7 pathway and oxidative stress. Nanocurcumin ameliorated hypoxia-induced hypertrophy and apoptosis in H9c2 cells significantly (p ≤ 0.01), by downregulating atrial natriuretic factor expression, caspase-3/-7 activation, oxidative stress and stabilizing hypoxia-inducible factor-1α (HIF-1α) better than curcumin. Nanocurcumin provides insight into its use as a potential candidate in curing hypoxia-induced cardiac pathologies by restoring oxidative balance.
authors.affiliation: Experimental Biology Division, Department of Experimental Biology, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Nehra
authors.forename: Varun
authors.initials: V
authors.lastname: Bhardwaj
authors.forename: Namita
authors.initials: N
authors.lastname: Kalra
authors.forename: Lilly
authors.initials: L
authors.lastname: Ganju
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Shweta
authors.initials: S
authors.lastname: Saxena
authors.forename: Deepika
authors.initials: D
authors.lastname: Saraswat
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006984:Hypertrophy / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D049329:Nanostructures / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3; D053179:Caspase 7; D003474:Curcumin
references.citation: Molecules. 2012 May 18;17(5):5972-87
references.pmid: 22609787
references.citation: Hypertension. 2007 Feb;49(2):241-8
references.pmid: 17190878
references.citation: Pharmacol Ther. 2012 Sep;135(3):337-54
references.pmid: 22750195
references.citation: Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2528-34
references.pmid: 16399861
references.citation: Methods Mol Biol. 1984;1:1-3
references.pmid: 20512668
references.citation: FASEB J. 2001 Nov;15(13):2445-53
references.pmid: 11689469
references.citation: Antioxid Redox Signal. 2007 Jun;9(6):623-52
references.pmid: 17511580
references.citation: J Cardiovasc Pharmacol. 2014 Oct;64(4):375-84
references.pmid: 24921631
references.citation: J Clin Microbiol. 1981 Mar;13(3):498-502
references.pmid: 6165737
references.citation: Cardiovasc Res. 2004 Aug 15;63(3):373-80
references.pmid: 15276462
references.citation: Cardiovasc Res. 2009 Feb 15;81(3):457-64
references.pmid: 19047340
references.citation: Cardiovasc Res. 2000 Jul;47(1):23-37
references.pmid: 10869527
references.citation: Cancer Cell Int. 2013 Apr 16;13:36
references.pmid: 23590596
references.citation: Life Sci. 2011 Aug 1;89(5-6):182-7
references.pmid: 21703281
references.citation: Lancet. 1994 Sep 10;344(8924):721-4
references.pmid: 7915779
references.citation: Biochem Pharmacol. 2002 Sep;64(5-6):1057-64
references.pmid: 12213605
references.citation: Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68
references.pmid: 23662605
references.citation: Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H975-84
references.pmid: 20601462
references.citation: J Nanobiotechnology. 2007 Apr 17;5:3
references.pmid: 17439648
references.citation: Anal Biochem. 1983 Oct 1;134(1):111-6
references.pmid: 6660480
references.citation: Cardiovasc Res. 2000 Feb;45(3):704-12
references.pmid: 10728392
references.citation: Mol Pharmacol. 2006 Nov;70(5):1664-71
references.pmid: 16880289
references.citation: In Vitro Cell Dev Biol Anim. 2011 Feb;47(2):125-31
references.pmid: 21082279
references.citation: Anal Biochem. 1976 Jul;74(1):214-26
references.pmid: 962076
references.citation: Mol Pharm. 2007 Nov-Dec;4(6):807-18
references.pmid: 17999464
references.citation: J Nanosci Nanotechnol. 2014 Jan;14(1):803-14
references.pmid: 24730299
references.citation: Biochim Biophys Acta. 2008 Apr;1780(4):673-9
references.pmid: 18178166
references.citation: Molecules. 2011 Jun 03;16(6):4567-98
references.pmid: 21642934
references.citation: Ann N Y Acad Sci. 2000;899:136-47
references.pmid: 10863535
references.citation: J Microbiol Methods. 2013 Mar;92(3):307-9
references.pmid: 23275136
references.citation: Circ Res. 1998 Jul 13;83(1):15-26
references.pmid: 9670914
references.citation: FASEB J. 2001 May;15(7):1181-6
references.pmid: 11344086
references.citation: Circ Res. 1998 Jun 15;82(11):1111-29
references.pmid: 9633912
references.citation: J Clin Invest. 2005 Mar;115(3):500-8
references.pmid: 15765131
references.citation: Circulation. 1998 Aug 25;98(8):794-9
references.pmid: 9727550
references.citation: Cancer Biol Ther. 2011 Mar 1;11(5):474-6
references.pmid: 21263231
references.citation: Biotechnol Adv. 2012 Jan-Feb;30(1):310-20
references.pmid: 21619927