دورية أكاديمية
Downregulation of PTEN Promotes Autophagy via Concurrent Reduction in Apoptosis in Cardiac Hypertrophy in PPAR α -/- Mice.
| العنوان: | Downregulation of PTEN Promotes Autophagy via Concurrent Reduction in Apoptosis in Cardiac Hypertrophy in PPAR α -/- Mice. |
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| المؤلفون: | Kumari R; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Ray AG; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Mukherjee D; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Chander V; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Kar D; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Kumar US; Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati, India., Bharadwaj P V P D; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Guwahati, India., Banerjee SK; Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati, India., Konar A; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Bandyopadhyay A; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India. |
| المصدر: | Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2022 Feb 11; Vol. 9, pp. 798639. Date of Electronic Publication: 2022 Feb 11 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101653388 Publication Model: eCollection Cited Medium: Print ISSN: 2297-055X (Print) Linking ISSN: 2297055X NLM ISO Abbreviation: Front Cardiovasc Med Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media S.A., [2014]- |
| مستخلص: | Cardiac hypertrophy is characterized by an increase in the size of the cardiomyocytes which is initially triggered as an adaptive response but ultimately becomes maladaptive with chronic exposure to different hypertrophic stimuli. Prolonged cardiac hypertrophy is often associated with mitochondrial dysfunctions and cardiomyocyte cell death. Peroxisome proliferator activated receptor alpha (PPAR α), which is critical for mitochondrial biogenesis and fatty acid oxidation, is down regulated in hypertrophied cardiomyocytes. Yet, the role of PPAR α in cardiomyocyte death is largely unknown. To assess the role of PPAR α in chronic hypertrophy, isoproterenol, a β-adrenergic receptor agonist was administered in PPAR α knock out (PPAR α -/- ) mice for 2 weeks and hypertrophy associated changes in cardiac tissues were observed. Echocardiographic analysis ensured the development of cardiac hypertrophy and compromised hemodynamics in PPAR α -/- mice. Proteomic analysis using high resolution mass spectrometer identified about 1,200 proteins enriched in heart tissue. Proteins were classified according to biological pathway and molecular functions. We observed an unexpected down regulation of apoptotic markers, Annexin V and p53 in hypertrophied heart tissue. Further validation revealed a significant down regulation of apoptosis regulator, PTEN, along with other apoptosis markers like p53, Caspase 9 and c-PARP. The autophagy markers Atg3, Atg5, Atg7, p62, Beclin1 and LC3 A/B were up regulated in PPAR α -/- mice indicating an increase in autophagy. Similar observations were made in a high cholesterol diet fed PPAR α -/- mice. The results were further validated in vitro using NRVMs and H9C2 cell line by blocking PPAR α that resulted in enhanced autophagosome formation upon hypertrophic stimulation. The results demonstrate that in the absence of PPAR α apoptotic pathway is inhibited while autophagy is enhanced. The data suggest that PPAR α signaling might act as a molecular switch between apoptosis and autophagy thereby playing a critical role in adaptive process in cardiac hypertrophy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Kumari, Ray, Mukherjee, Chander, Kar, Kumar, Bharadwaj P.V.P., Banerjee, Konar and Bandyopadhyay.) |
| References: | Circulation. 2010 Dec 21;122(25):2727-35. (PMID: 21173361) Front Pharmacol. 2020 Nov 30;11:585163. (PMID: 33328989) Circulation. 2004 Apr 6;109(13):1580-9. (PMID: 15066961) Antioxid Redox Signal. 2019 Feb 10;30(5):713-732. (PMID: 29631413) PPAR Res. 2008;2008:253817. (PMID: 18288281) Aging (Albany NY). 2019 Sep 4;11(17):6872-6891. (PMID: 31484164) Alzheimers Res Ther. 2013 Sep 26;5(5):42. (PMID: 24074163) Cell Metab. 2017 May 2;25(5):1012-1026. (PMID: 28467921) Cell Rep. 2019 Mar 19;26(12):3323-3335.e4. (PMID: 30893604) Physiol Rev. 2011 Jul;91(3):1023-70. (PMID: 21742795) J Am Heart Assoc. 2019 Jun 18;8(12):e012673. (PMID: 31185774) J Mol Cell Cardiol. 2009 Feb;46(2):193-200. (PMID: 19038262) J Mol Cell Cardiol. 2012 Aug;53(2):240-9. (PMID: 22609523) Nat Commun. 2017 Nov 15;8(1):1508. (PMID: 29142193) J Clin Invest. 2006 Jun;116(6):1467-70. (PMID: 16741569) Cancer Cell. 2006 Jul;10(1):51-64. (PMID: 16843265) Front Pharmacol. 2020 Aug 14;11:1255. (PMID: 32922293) Oncogene. 2003 Dec 8;22(56):9030-40. (PMID: 14663481) Oncotarget. 2017 Apr 4;8(14):23996-24008. (PMID: 28177918) Nat Rev Cardiol. 2018 Jul;15(7):387-407. (PMID: 29674714) Mol Med Rep. 2015 Dec;12(6):7899-906. (PMID: 26497978) Oxid Med Cell Longev. 2017;2017:3920195. (PMID: 28751931) Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10140-5. (PMID: 9707614) J Biomed Res. 2013 Jul;27(4):254-71. (PMID: 23885265) Curr Hypertens Rep. 2009 Dec;11(6):406-11. (PMID: 19895751) Ernst Schering Found Symp Proc. 2007;(4):23-34. (PMID: 18811051) J Cardiovasc Pharmacol. 2009 Oct;54(4):327-34. (PMID: 19687748) Cell Death Differ. 2009 Jan;16(1):46-56. (PMID: 18636076) J Cell Biochem. 2004 Aug 15;92(6):1141-59. (PMID: 15258898) Biomed Res Int. 2014;2014:616149. (PMID: 25197653) Cell Death Dis. 2019 May 24;10(6):403. (PMID: 31127082) Circ Res. 2007 Feb 16;100(3):e45-6. (PMID: 17307965) Nat Rev Drug Discov. 2017 Jul;16(7):487-511. (PMID: 28529316) Circ Res. 2000 Jun 9;86(11):1107-13. (PMID: 10850960) Circ Res. 2017 May 26;120(11):1812-1824. (PMID: 28546358) Biomed Res Int. 2016;2016:9583268. (PMID: 28101515) Circ Res. 1989 Sep;65(3):657-70. (PMID: 2527639) Circulation. 2015 Apr 21;131(16):1435-47. (PMID: 25901069) Am J Physiol Heart Circ Physiol. 2017 Sep 1;313(3):H584-H596. (PMID: 28646024) Cell Death Differ. 2018 Jan;25(1):104-113. (PMID: 29149101) Biochim Biophys Acta. 2013 Apr;1833(4):840-7. (PMID: 22964268) Int J Biol Sci. 2015 Apr 27;11(6):672-8. (PMID: 25999790) J Biol Chem. 2000 Mar 10;275(10):7337-42. (PMID: 10702305) Acta Biochim Biophys Sin (Shanghai). 2016 Jun;48(6):491-500. (PMID: 27084518) Annu Rev Biochem. 2014;83:641-69. (PMID: 24905788) Cell Metab. 2011 Nov 2;14(5):598-611. (PMID: 22055503) Circ Heart Fail. 2014 Jul;7(4):680-91. (PMID: 25028350) J Appl Physiol (1985). 2013 Jan 1;114(1):131-47. (PMID: 23104696) Cardiovasc Pathol. 2016 Mar-Apr;25(2):103-12. (PMID: 26764143) |
| فهرسة مساهمة: | Keywords: PPAR α; PTEN; apoptosis; autophagy; cardiac hypertrophy |
| تواريخ الأحداث: | Date Created: 20220228 Latest Revision: 20220301 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8881053 |
| DOI: | 10.3389/fcvm.2022.798639 |
| PMID: | 35224041 |
| قاعدة البيانات: | MEDLINE |
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