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Triiodo-L-thyronine (T3) downregulates Npr1 gene (coding for natriuretic peptide receptor-A) transcription in H9c2 cells: involvement of β-AR-ROS signaling

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Abstract

Introduction

Natriuretic peptide receptor-A (NPR-A) signaling system is considered as an intrinsic productive mechanism of the heart that opposes abnormal cardiac remodeling and hypertrophic growth. NPR-A is coded by Npr1 gene, and its expression is downregulated in the hypertrophied heart.

Aim

We sought to examine the levels of Npr1 gene transcription in triiodo-L-thyronine (T3) treated hypertrophied cardiomyocyte (H9c2) cells, in vitro, and also the involvement of β-adrenergic receptor (β-AR) - Reactive oxygen species (ROS) signaling system in the down-regulation of Npr1 transcription also studied.

Main methods

Anti-hypertrophic Npr1 gene transcription was monitored in control and T3-treated (dose and time dependent) H9c2 cells, using a real time PCR method. Further, cell size, intracellular cGMP, ROS, hypertrophy markers (ANP, BNP, α-sk, α-MHC and β-MHC), β-AR, and protein kinase cGMP-dependent 1 (PKG-I) genes expression were also determined. The intracellular cGMP and ROS levels were determined by ELISA and DCF dye method, respectively. In addition, to neutralize T3 mediated ROS generation, H9c2 cells were treated with T3 in the presence and absence of antioxidants [curcumin (CU) or N-acetyl-L-cysteine (NAC)].

Results

A dose dependent (10 pM, 100 pM, 1 nM and 10 nM) and time dependent (12 h, 24 h and 48 h) down-regulation of Npr1 gene transcription (20, 39, 60, and 74% respectively; 18, 55, and 85%, respectively) were observed in T3-treated H9c2 cells as compared with control cells. Immunofluorescence analysis also revealed that a marked down regulation of NPR- A protein in T3-treated cells as compared with control cells. Further, a parallel downregulation of cGMP and PKG-I (2.4 fold) were noticed in the T3-treated cells. In contrast, a time dependent increased expression of β-AR (60, 72, and 80% respectively) and ROS (26, 48, and 74%, respectively) levels were noticed in T3-treated H9c2 cells as compared with control cells. Interestingly, antioxidants, CU or NAC co-treated T3 cells displayed a significant reduction in ROS (69 and 81%, respectively) generation and to increased Npr1 gene transcription (81 and 88%, respectively) as compared with T3 alone treated cells.

Conclusion

Our result suggest that down regulation of Npr1 gene transcription is critically involved in T3- induced hypertrophic growth in H9c2 cells, and identifies the cross-talk between T3-β-AR-ROS and NPR-A signaling.

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References

  1. Y. Takahashi, T. Nakayama, M. Soma, Y. Izumi, K. Kanmatsuse, Organization of the Human Natriuretic Peptide Receptor A Gene. Biochem. Biophys. Res. Commun. 246(3), 736–739 (1998). https://doi.org/10.1006/bbrc.1998.8693

    Article  CAS  PubMed  Google Scholar 

  2. D.G. Lowe, M.S. Chang, R. Hellmiss, E. Chen, S. Singh, D.L. Garbers, D.V. Goeddel, Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction. EMBO J. 8(5), 1377–1384 (1989). https://doi.org/10.1002/j.1460-2075.1989.tb03518.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. D.L. Garbers, Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands. Cell 71(1), 1–4 (1992). https://doi.org/10.1016/0092-8674(92)90258-e

    Article  CAS  PubMed  Google Scholar 

  4. K.N. Pandey, Biology of natriuretic peptides and their receptors. Peptides 26(6), 901–932 (2005). https://doi.org/10.1016/j.peptides.2004.09.024

    Article  CAS  PubMed  Google Scholar 

  5. L.R. Potter, T. Hunter, Phosphorylation of the Kinase Homology Domain Is Essential for Activation of the A-Type Natriuretic Peptide Receptor. Mol. Cell. Biol. 18(4), 2164–2172 (1998). https://doi.org/10.1128/mcb.18.4.2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. I. Mani, K.N. Pandey, Emerging concepts of receptor endocytosis and concurrent intracellular signaling: Mechanisms of guanylyl cyclase/natriuretic peptide receptor-A activation and trafficking. Cell Signal 60, 17–30 (2019). https://doi.org/10.1016/j.cellsig.2019.03.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. V. Cannone, A. Cabassi, R. Volpi, J.C. Burnett, Atrial natriuretic peptide: a molecular target of novel therapeutic approaches to cardio-metabolic disease. Int. J. Mol. Sci. 20(13), 3265 (2019). https://doi.org/10.3390/ijms20133265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. I. Kishimoto, T. Tokudome, K. Nakao, K. Kangawa, Natriuretic peptide system: an overview of studies using genetically engineered animal models. FEBS J. 278(11), 1830–1841 (2011). https://doi.org/10.1111/j.1742-4658.2011.08116.x

    Article  CAS  PubMed  Google Scholar 

  9. E. Vellaichamy, M.L. Khurana, J. Fink, K.N. Pandey, Involvement of the NF-kappa B/matrix metalloproteinase pathway in cardiac fibrosis of mice lacking guanylyl cyclase/natriuretic peptide receptor A. J. Biol. Chem. 280(19), 19230–19242 (2005). https://doi.org/10.1074/jbc.m411373200

    Article  CAS  PubMed  Google Scholar 

  10. P.M. Oliver, J.E. Fox, R. Kim, H.A. Rockman, H.S. Kim, R.L. Reddick, K.N. Pandey, S.L. Milgram, O. Smithies, N. Maeda, Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proc. Natl Acad. Sci. USA 94(26), 14730–5 (1997). https://doi.org/10.1073/pnas.94.26.14730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. L.J. Ellmers, J.W. Knowles, H.S. Kim, O. Smithies, N. Maeda, V.A. Cameron, Ventricular expression of natriuretic peptides in Npr1(-/-) mice with cardiac hypertrophy and fibrosis. Am. J. Physiol. Heart Circ. Physiol. 283(2), H707–14 (2002). https://doi.org/10.1152/ajpheart.00677.2001

    Article  CAS  PubMed  Google Scholar 

  12. E. Vellaichamy, D. Zhao, N. Somanna, K.N. Pandey, Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A up-regulates ACE and AT1 receptor gene expression and signaling: role in cardiac hypertrophy. Physiol. Genomics 31(12), 193–202 (2007). https://doi.org/10.1152/physiolgenomics.00079.2007

    Article  CAS  PubMed  Google Scholar 

  13. D. Zhao, E. Vellaichamy, N. Somanna, K.N. Pandey, Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels. Am. J. Physiol. Renal Physiol. 293(1), F121–F127 (2007). https://doi.org/10.1152/ajprenal.00478.2006

    Article  CAS  PubMed  Google Scholar 

  14. S. Rubattu, G. Bigatti, A. Evangelista, C. Lanzani, R. Stanzione, L. Zagato, P. Manunta, S. Marchitti, V. Venturelli, G. Bianchi, M. Volpe, P. Stella, Association of atrial natriuretic peptide and type a natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension. J. Am. Coll. Cardiol. 48(3), 499–505 (2006). https://doi.org/10.1016/j.jacc.2005.12.081

    Article  CAS  PubMed  Google Scholar 

  15. J. Wang, Z. Wang, C. Yu, Association of Polymorphisms in the Atrial Natriuretic Factor Gene with the Risk of Essential Hypertension: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health. 13(5), 458 (2016). https://doi.org/10.3390/ijerph13050458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. V. Gopi, V. Subramanian, S. Manivasagam, E. Vellaichamy, Angiotensin II down- regulates natriuretic peptide receptor-A expression and guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells: role of ROS and NF-kB. Mol. Cell Biochem. 409(1-2), 67–79 (2015). https://doi.org/10.1007/s11010-015-2513-0

    Article  CAS  PubMed  Google Scholar 

  17. W. Song, H. Wang, Q. Wu, Atrial natriuretic peptide in cardiovascular biology and disease (NPPA). Gene 569(1), 1–6 (2015). https://doi.org/10.1016/j.gene.2015.06.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. S. Manivasagam, E. Vellaichamy, Suppression of Npr1, not Npr2 gene function induces hypertrophic growth in H9c2 cells in vitro. Biochem. Biophys. Res. Commun. 491(2), 250–256 (2017). https://doi.org/10.1016/j.bbrc.2017.07.123

    Article  CAS  PubMed  Google Scholar 

  19. S. Manivasagam, V. Subramanian, A. Tumala, E. Vellaichamy, Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats. Mol. Cell Endocrinol. 433, 117–29 (2016). https://doi.org/10.1016/j.mce.2016.06.010

    Article  CAS  PubMed  Google Scholar 

  20. P. Kumar, R. Garg, G. Bolden, K.N. Pandey, Interactive roles of Ets-1, Sp1, and acetylated histones in the retinoic acid-dependent activation of guanylyl cyclase/atrial natriuretic peptide receptor-A gene transcription. J. Biol. Chem. 285(48), 37521–30 (2010). https://doi.org/10.1074/jbc.M110.132795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. U. Subramanian, P. Kumar, I. Mani, D. Chen, I. Kessler, R. Periyasamy, G. Raghavaraju, K. Pandey, Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice. Physiol. Genomics 48(7), 477–490 (2016). https://doi.org/10.1152/physiolgenomics.00073.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. S. Manivasagam, T. Velusamy, B. Sowndharajan, N. Chandrasekar, S. Dhanusu, E. Vellaichamy, Valporic acid enhances the Atrial Natriuretic Peptide (ANP) mediated anti-hypertrophic activity by modulating the Npr1 gene transcription in H9c2 cells in vitro. Eur. J. Pharmacol. 813, 94–104 (2017). https://doi.org/10.1016/j.ejphar.2017.07.042

    Article  CAS  PubMed  Google Scholar 

  23. I. Klein, S. Danzi, Thyroid disease and the heart. Circulation 116(15), 1725–1735 (2007). https://doi.org/10.1161/CIRCULATIONAHA.106.678326

    Article  PubMed  Google Scholar 

  24. S. Danzi, I. Klein, Thyroid disease and the cardiovascular system. Endocrinol. Metab. Clin. N. Am. 43(2), 517–528 (2014). https://doi.org/10.1016/j.ecl.2014.02.005

    Article  Google Scholar 

  25. A. Jabbar, A. Pingitore, S.H. Pearce, A. Zaman, G. Iervasi, S. Razvi, Thyroid hormones and cardiovascular disease. Nat. Rev. Cardiol. 14(1), 39–55 (2017). https://doi.org/10.1038/nrcardio.2016.174

    Article  CAS  PubMed  Google Scholar 

  26. C.W. Siu, C.Y. Yeung, C.P. Lau, A.W.C. Kung, H.F. Tse, Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism. Heart 93(4), 483–487 (2010). https://doi.org/10.1136/hrt.2006.100628

    Article  Google Scholar 

  27. B. Biondi, Mechanisms in endocrinology. Heart failure and thyroid dysfunction. Eur. J. Endocrinol. 167(5), 609–18 (2012). https://doi.org/10.1530/EJE-12-0627

    Article  CAS  PubMed  Google Scholar 

  28. J.E. Mitchell, A.S. Hellkamp, D.B. Mark, J. Anderson, G.W. Johnson, J.E. Poole, K.L. Lee, G.H. Bardy, Thyroid function in heart failure and impact on mortality. JACC Heart Fail 1(1), 48–55 (2013). https://doi.org/10.1016/j.jchf.2012.10.004

    Article  PubMed  PubMed Central  Google Scholar 

  29. J.P. Bilezikian, J.N. Loeb, The influence of hyperthyroidism and hypothyroidism on α- and β-adrenergic receptor systems and adrenergic responsiveness. Endocr. Rev. 41(4), 378–387 (1983). https://doi.org/10.1210/edrv-4-4-378

    Article  Google Scholar 

  30. L.W. Hu, L.A. Benvenuti, E.A. Liberti, M.S. Carneiro‐Ramos, M.L.M. Barreto‐Chaves, Thyroxine‐induced cardiac hypertrophy:Influence of adrenergic nervous system versus renin‐angiotensin system on myocyte remodeling. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285(6), 1473–1480 (2003). https://doi.org/10.1152/ajpregu.00269.2003

    Article  Google Scholar 

  31. W. Dillmann, Cardiac hypertrophy and thyroid hormone signaling. Heart Fail. Rev. 15(2), 125–132 (2010). https://doi.org/10.1007/s10741-008-9125-7

    Article  CAS  PubMed  Google Scholar 

  32. A.P.C. Takano, N. Senger, C.D. Munhoz, M.L.M. Barreto‐Chaves, AT1 blockage impairs NF‐kB activation mediated by thyroid hormone in cardiomyocytes. Pflugers Archiv 470(3), 549–558 (2018). https://doi.org/10.1007/s00424-017-2088-6

    Article  CAS  PubMed  Google Scholar 

  33. M.S. Carneiro‐Ramos, G.P. Diniz, A.P. Nadu, J. Almeida, R.L.P. Vieira, R.A.S. Santos, M.L.M. Barreto‐Chaves, Blockage of angiotensin II type 2 receptor prevents thyroxine‐mediated cardiac hypertrophy by blocking Akt activation. Basic Res. Cardiol. 105(3), 325–335 (2010). https://doi.org/10.1007/s00395-010-0089-0

    Article  CAS  PubMed  Google Scholar 

  34. A. Parthasarathy, V. Gopi, S. Umadevi, A. Simna, M.J.U. Sheik, H. Divya, E. Vellaichamy, Suppression of atrial natriuretic peptide/natriuretic peptide receptor-A- mediated signaling up-regulates angiotensin-II-induced collagen synthesis in adult cardiac fibroblasts. Mol. Cell Biochem. 378(1-2), 217–228 (2013). https://doi.org/10.1007/s11010-013-1612-z

    Article  CAS  PubMed  Google Scholar 

  35. G. Sacripanti, M. Nguyen, L. Lorenzini, S. Frascarelli, A. Saba, R. Zucchi, S. Ghelardoni, 3,5-Diiodo-l-Thyronine Increases Glucose Consumption in Cardiomyoblasts Without Affecting the Contractile Performance in Rat Heart. Front. Endocrinol. 30(9), 282 (2018). https://doi.org/10.3389/fendo.2018.00282

    Article  Google Scholar 

  36. A. Rozanski, A.P.C. Takano, P.N. Kato, A.G. Soares, C. Lellis-Santos, J.C. Campos, J.C.B. Ferreira, M.L.M. Barreto-Chaves, A.S. Moriscot, M-protein is down-regulated in cardiac hypertrophy driven by thyroid hormone in rats. Mol. Endocrinol. 27(12), 2055–65 (2013). https://doi.org/10.1210/me.2013-1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. S.M. Chacko, K.G. Nevin, R. Dhanyakrishnan, B.P. Kumar, Protective effect of p-coumaric acid against doxorubicin induced toxicity in H9c2 cardiomyoblast cell lines. Toxicol. Rep. 2, 1213–1221 (2015). https://doi.org/10.1016/j.toxrep.2015.08.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. J.H. Lee, D.H. Kim, M.A. Kim, K.H. Jung, K.H. Lee, Mitochondrial ROS-Mediated Metabolic and Cytotoxic Effects of Isoproterenol on Cardiomyocytes Are p53-Dependent and Reversed by Curcumin. Molecules 27(4), 1346 (2022). https://doi.org/10.3390/molecules27041346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 7(72), 248–54 (1976). https://doi.org/10.1006/abio.1976.9999

    Article  Google Scholar 

  40. J.W. Knowles, G. Esposito, L. Mao, J.R. Hagaman, J.E. Fox, O. Smithies, H.A. Rockman, N. Maeda, Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient. mice. J. Clin. Invest. 107(8), 975–984 (2001). https://doi.org/10.1172/jci11273

    Article  CAS  PubMed  Google Scholar 

  41. I. Kishimoto, K. Rossi, D.L. Garbers, A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Proc. Natl Acad. Sci. USA 98(5), 2703–2706 (2001). https://doi.org/10.1073/pnas.051625598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. M.L. Barreto-Chaves, N. Senger, M. Fevereiro, A.C. Parletta, A. Takano, Impact of hyperthyroidism on cardiac hypertrophy. Endocr. Connect. 9(3), R59–69 (2020). https://doi.org/10.1530/EC-19-0543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. S. Ventrella, I. Klein, Beta-adrenergic receptor blocking drugs in the management of hyperthyroidism. Endocrinologist 4(5), 391–399 (1994). https://doi.org/10.1097/00019616-199409000-00010

    Article  Google Scholar 

  44. R.D. Utiger, β-Adrenergic-antagonist therapy for hyperthyroid Graves’ disease. N. Engl. J. Med 310(24), 1597–1598 (1984). https://doi.org/10.1056/NEJM198406143102410

    Article  CAS  PubMed  Google Scholar 

  45. I. Klein, K. Ojamaa, Thyroid hormone and the cardiovascular system. N. Engl. J. Med. 344(7), 501–509 (2001). https://doi.org/10.1056/NEJM200102153440707

    Article  CAS  PubMed  Google Scholar 

  46. H.A. Rockman, W.J. Koch, R.J. Lefkowitz, Seven-transmembrane-spanning receptors and heart function. Nature 415(68), 206–12 (2002). https://doi.org/10.1038/415206a

    Article  CAS  PubMed  Google Scholar 

  47. A.S.R. Araujo, G.P. Diniz, F.E.R. Seibel, G. Branchini, M.F.M. Ribeiro, I.S. Brum, N. Khaper, M.L.M. Barreto-Chaves, A.B. Bello-Klein, Reactive oxygen and nitrogen species balance in the determination of thyroid hormones-induced cardiac hypertrophy mediated by renin- angiotensin system. Mol. Cell Endocrinol. 333(1), 78–84 (2011). https://doi.org/10.1016/j.mce.2010.12.018

    Article  CAS  PubMed  Google Scholar 

  48. H. Yaomeng, L. Tongxin, G. Shichao, L. Shuyu, Z. Xiaoran, L. Ying, L. Dangyang, L. Weimin, L. Yang, L. Kunshen, Z. Zheng, L. Chao, Investigating the Role of NPR1 in Dilated Cardiomyopathy and its Potential as a Therapeutic Target for Glucocorticoid Therapy. Front. Pharmacol. 14, 1290253 (2023). https://doi.org/10.3389/fphar.2023.1290253

    Article  CAS  Google Scholar 

  49. C. Nunn, M.X. Zou, A.J. Sobiesiak, A.A. Roy, L. Kirshenbaum, P. Chidiac, RGS2 inhibits β-adrenergic receptor-induced cardiomyocyte hypertrophy. Cell Signal 22(8), 1231–1239 (2010). https://doi.org/10.1016/j.cellsig.2010.03.015

    Article  CAS  PubMed  Google Scholar 

  50. G.X. Zhang, S. Kimura, A. Nishiyama, T. Shokoji, M. Rahman, L. Yao, Y. Abe, Cardiac oxidative stress in acute and chronic isoproterenol-infused rats. Cardiovasc. Res. 65(1), 230e238 (2005). https://doi.org/10.1016/j.cardiores.2004.08.013

    Article  CAS  Google Scholar 

  51. P. Venditti, S. Di. Meo, Thyroid hormone-induced oxidative stress. Cell. Mol. Life Sci 63(4), 414–434 (2006). https://doi.org/10.1007/s00018-005-5457-9

  52. G.P. Diniz, M.S. Carneiro-Ramos, M.L.M. Barreto-Chaves, Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK- 3beta/mTOR signaling pathway. Basic Res. Cardiol. 104(6), 653–67 (2009). https://doi.org/10.1007/s00395-009-0043-1

    Article  CAS  PubMed  Google Scholar 

  53. C.H. Huang, F.T. Wang, Y.D. Hsuuw, F.J. Huang, W.H. Chan, Non-embryotoxic dosage of alternariol aggravates ochratoxin A-triggered deleterious effects on embryonic development through ROS-dependent apoptotic processes. Toxicol. Res. 10(6), 1211–1222 (2021). https://doi.org/10.1093/toxres/tfab112

    Article  Google Scholar 

  54. Y. Zhang, S. Su, W. Li, Y. Ma, J. Shen, Y. Wang, Y. Shen, J. Chen, Y. Ji, Y. Xie, H. Ma, M. Xiang, Piezo1-Mediated Mechanotransduction Promotes Cardiac Hypertrophy by Impairing Calcium Homeostasis to Activate Calpain/Calcineurin Signaling. Hypertension 78(3), 647–660 (2021). https://doi.org/10.1161/HYPERTENSIONAHA.121.17177

    Article  CAS  PubMed  Google Scholar 

  55. A. Kaumann, S. Bartel, P. Molenaar, L. Sanders, K. Burrell, D. Vetter, P. Hempel, P. Karczewski, E. Krause, Activation of β2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C protein in ventricular myocardium from patients with terminal heart failure. Circulation 99(1), 65–72 (1999). https://doi.org/10.1161/01.cir.99.1.65

    Article  CAS  PubMed  Google Scholar 

  56. W. Dillmann, Cellular action of thyroid hormone on the heart. Thyroid 12(6), 447–52 (2002). https://doi.org/10.1089/105072502760143809

    Article  CAS  PubMed  Google Scholar 

  57. F. Vargas, J. Moreno, I. Rodriguez-Gomez, R. Wangensteen, A. Osuna, M. Alvarez-Guerra, J. Garcia-Estan, Vascular and renal function in experimental thyroid disorders. Eur. J. Endocrinol. 154(2), 197–212 (2006). https://doi.org/10.1530/eje.1.02093

    Article  CAS  PubMed  Google Scholar 

  58. F. Cioffi, R. Senese, A. Lanni, F. Goglia, Thyroid hormones and mitochondria: with a brief look at derivatives and analogues. Mol. Cell Endocrinol. 379(1), 51–61 (2013). https://doi.org/10.1016/j.mce.2013.06.006

    Article  CAS  PubMed  Google Scholar 

  59. T. Ines, G. Benjamin, J. Angelo, B. Doruntina, R. Rene, O. Barbara, F. Wolfgang, T. Corina, T3-induced enhancement of mitochondrial Ca2+ uptake as a boost for mitochondrial metabolism. Free Radical Biol. Med 181, 197–208 (2022). https://doi.org/10.1016/j.freeradbiomed.2022.01.024

    Article  CAS  Google Scholar 

  60. T. Ide, H. Tsutsui, S. Hayashidani, D. Kang, N. Suematsu, K. Nakamura, A. Takeshita, Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction. Circ. Res. 88(5), 529–535 (2001). https://doi.org/10.1161/01.res.88.5.529

    Article  CAS  PubMed  Google Scholar 

  61. D.M. Deborah, L.R. Lincoln, Dendroaspis natriuretic peptide and the designer natriuretic peptide, CD-NP, are resistant to proteolytic inactivation. J. Mol. Cell. Cardiol. 51(1), 0–71 (2011). https://doi.org/10.1016/j.yjmcc.2011.03.013

    Article  CAS  Google Scholar 

  62. E.J. Tsai, D.A. Kass, Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol. Ther. 122(3), 216–38 (2009). https://doi.org/10.1016/j.pharmthera.2009.02.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. N. Senger, M. Melo, G. Diniz, M. Campagnole-Santos, R. Santos, M. Barreto-Chaves, Angiotensin-(1-7) reduces cardiac effects of thyroid hormone by GSK3Β/NFATc3 signaling pathway. Clin. Sci. 132(11), 1117–1133 (2018). https://doi.org/10.1042/CS20171606

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Dr. N. Dhatchanamoorthy for the support during this study. This study was supported by RUSA 2.0 - University of Madras (T1 PF6).

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  1. Peptide Research and Molecular Cardiology Unit, Department of Biochemistry, University of Madras, Guindy campus, Chennai, Tamil Nadu, 600025, India

    Gopinath Nagaraj & Elangovan Vellaichamy

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Study design: E.V. Collection of data: G.N. interpretation of data: E.V. Authors participate in drafting the article: G.N. and E.V. Revising it critically for important intellectual content: E.V. Final approval of the version to be published: All authors.

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Nagaraj, G., Vellaichamy, E. Triiodo-L-thyronine (T3) downregulates Npr1 gene (coding for natriuretic peptide receptor-A) transcription in H9c2 cells: involvement of β-AR-ROS signaling. Endocrine (2024). https://doi.org/10.1007/s12020-024-03849-6

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