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Catestatin reverses the hypertrophic effects of norepinephrine in H9c2 cardiac myoblasts by modulating the adrenergic signaling

  • Md. Jahangir Alam
  • Richa Gupta
  • Nitish R. Mahapatra
  • Shyamal K. GoswamiEmail author
Article
  • 32 Downloads

Abstract

Catestatin (CST) is a catecholamine release-inhibitory peptide secreted from the adrenergic neurons and the adrenal glands. It regulates the cardiovascular functions and it is associated with cardiovascular diseases. Though its mechanisms of actions are not known, there are evidences of cross-talk between the adrenergic and CST signaling. We hypothesized that CST moderates the adrenergic overdrive and studied its effects on norepinephrine-mediated hypertrophic responses in H9c2 cardiac myoblasts. CST alone regulated the expression of a number of fetal genes that are induced during hypertrophy. When cells were pre-treated CST, it blunted the modulation of those genes by norepinephrine. Norepinephrine (2 µM) treatment also increased cell size and enhanced the level of Troponin T in the sarcomere. These effects were attenuated by the treatment with CST. CST attenuated the immediate generation of ROS and the increase in glutathione peroxidase activity induced by norepinephrine treatment. Expression of fosB and AP-1 promoter–reporter constructs was used as the endpoint readout for the interaction between the CST and adrenergic signals at the gene level. It showed that CST largely attenuates the stimulatory effects of norepinephrine and other mitogenic signals through the modulation of the gene regulatory modules in a characteristic manner. Depending upon the dose, the signaling by CST appears to be disparate, and at 10–25 nM doses, it primarily moderated the signaling by the β1/2-adrenoceptors. This study, for the first time, provides insights into the modulation of adrenergic signaling in the heart by CST.

Keywords

Catestatin Cardiac myocyte Adrenergic signaling Hypertrophy Apoptosis Reactive oxygen species 

Abbreviations

Acta1

Actin, alpha 1

AP-1

Activator protein 1

ANP

Atrial natriuretic peptide

AR

Adrenergic receptor

cAMP

Cyclic adenosine monophosphate

CEBP

CCAAT/enhancer binding protein

cGMP

Cyclic guanosine monophosphate

CHGA

Chromogranin A

CST

Catestatin

DCFH-DA

Dichloro-dihydro-fluorescein diacetate

DHE

Dihydroethidium

eNOS

Endothelial nitric oxide synthase

FosB

FBJ osteosarcoma oncogene B

GPx

Glutathione peroxidase

HPF

Hydroxyphenylfluorescein

ISO

Isoproterenol

MAP

Mitogen-activated protein

MHC

Myosin heavy chain

PDE2

Phosphodiesterase 2

PI3-kinase

Phosphoinositide 3-kinase

PKA

Protein kinase A

ROS

Reactive oxygen species

SOD

Superoxide dismutase

SP-1

Specificity protein 1

Notes

Acknowledgements

The authors thankfully acknowledge the funding supports from the Department of Biotechnology [DBT], Government of India (BT/PR4268/BRB/10/1016/2011 awarded to SKG; BT/PR12820/ BRB/10/726/2009 to NRM). Partial support also came from the DST-PURSE funding support to the Jawaharlal Nehru University. MJA is a recipient of JR/SR Fellowship from DBT, Government of India.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

11010_2019_3661_MOESM1_ESM.pptx (393 kb)
Supplementary material 1 (PPTX 393 kb)
11010_2019_3661_MOESM2_ESM.docx (16 kb)
Supplementary material 2 (DOCX 16 kb)
11010_2019_3661_MOESM3_ESM.docx (12 kb)
Supplementary material 3 (DOCX 12 kb)

References

  1. 1.
    Fothergill LJ, Callaghan B, Hunne B et al (2017) Costorage of enteroendocrine hormones evaluated at the cell and subcellular levels in male mice. Endocrinology 158:2113–2123.  https://doi.org/10.1210/en.2017-00243 CrossRefPubMedGoogle Scholar
  2. 2.
    Troger J, Theurl M, Kirchmair R et al (2017) Granin-derived peptides. Prog Neurobiol 154:37–61.  https://doi.org/10.1016/j.pneurobio.2017.04.003 CrossRefPubMedGoogle Scholar
  3. 3.
    Bandyopadhyay GK, Mahata SK (2017) Chromogranin A regulation of obesity and peripheral insulin sensitivity. Front Endocrinol Lausanne 8:20.  https://doi.org/10.3389/fendo.2017.00020 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Helle KB, Corti A (2015) Chromogranin A: a paradoxical player in angiogenesis and vascular biology. Cell Mol Life Sci CMLS 72:339–348.  https://doi.org/10.1007/s00018-014-1750-9 CrossRefPubMedGoogle Scholar
  5. 5.
    Tota B, Angelone T, Cerra MC (2014) The surging role of Chromogranin A in cardiovascular homeostasis. Front Chem 2:64.  https://doi.org/10.3389/fchem.2014.00064 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Helle KB, Metz-Boutigue M-H, Cerra MC, Angelone T (2018) Chromogranins: from discovery to current times. Pflug Arch 470:143–154.  https://doi.org/10.1007/s00424-017-2027-6 CrossRefGoogle Scholar
  7. 7.
    Goetze JP, Alehagen U, Flyvbjerg A, Rehfeld JF (2014) Chromogranin A as a biomarker in cardiovascular disease. Biomark Med 8:133–140.  https://doi.org/10.2217/bmm.13.102 CrossRefPubMedGoogle Scholar
  8. 8.
    Goetze JP, Hilsted LM, Rehfeld JF, Alehagen U (2014) Plasma chromogranin A is a marker of death in elderly patients presenting with symptoms of heart failure. Endocr Connect 3:47–56.  https://doi.org/10.1530/EC-14-0017 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gayen JR, Gu Y, O’Connor DT, Mahata SK (2009) Global disturbances in autonomic function yield cardiovascular instability and hypertension in the chromogranin a null mouse. Endocrinology 150:5027–5035.  https://doi.org/10.1210/en.2009-0429 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Vaingankar SM, Li Y, Biswas N et al (2010) Effects of chromogranin A deficiency and excess in vivo: biphasic blood pressure and catecholamine responses. J Hypertens 28:817–825.  https://doi.org/10.1097/HJH.0b013e328336ed3e CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Borges R, Dominguez N, Smith CB et al (2013) Granins and catecholamines: functional interaction in chromaffin cells and adipose tissue. Adv Pharmacol 68:93–113.  https://doi.org/10.1016/B978-0-12-411512-5.00005-1 CrossRefPubMedGoogle Scholar
  12. 12.
    Loh YP, Cheng Y, Mahata SK et al (2012) Chromogranin A and derived peptides in health and disease. J Mol Neurosci MN 48:347–356.  https://doi.org/10.1007/s12031-012-9728-2 CrossRefPubMedGoogle Scholar
  13. 13.
    Mahata SK, Kiranmayi M, Mahapatra NR (2017) Catestain: a master regulator of cardiovascular functions. Curr Med Chem.  https://doi.org/10.2174/0929867324666170425100416 CrossRefGoogle Scholar
  14. 14.
    Montesinos MS, Machado JD, Camacho M et al (2008) The crucial role of chromogranins in storage and exocytosis revealed using chromaffin cells from CHROMOGRANIN A null mouse. J Neurosci 28:3350–3358.  https://doi.org/10.1523/JNEUROSCI.5292-07.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bandyopadhyay GK, Vu CU, Gentile S et al (2012) Catestatin (chromogranin A(352–372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling. J Biol Chem 287:23141–23151.  https://doi.org/10.1074/jbc.M111.335877 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wang D, Liu T, Shi S et al (2016) Chronic administration of catestatin improves autonomic function and exerts cardioprotective effects in myocardial infarction rats. J Cardiovasc Pharmacol Ther 21:526–535.  https://doi.org/10.1177/1074248416628676 CrossRefPubMedGoogle Scholar
  17. 17.
    Wu Z, Zhu D (2014) The important role of catestatin in cardiac remodeling. Biomark Biochem Indic Expo Response Susceptibility Chem 19:625–630.  https://doi.org/10.3109/1354750X.2014.950331 CrossRefGoogle Scholar
  18. 18.
    Angelone T, Quintieri AM, Pasqua T et al (2015) The NO stimulator, Catestatin, improves the Frank–Starling response in normotensive and hypertensive rat hearts. Nitric Oxide 50:10–19.  https://doi.org/10.1016/j.niox.2015.07.004 CrossRefPubMedGoogle Scholar
  19. 19.
    Fung MM, Salem RM, Mehtani P et al (2010) Direct vasoactive effects of the chromogranin A (CHGA) peptide catestatin in humans in vivo. Clin Exp Hypertens 32:278–287.  https://doi.org/10.3109/10641960903265246 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Theurl M, Schgoer W, Albrecht K et al (2010) The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. Circ Res 107:1326–1335.  https://doi.org/10.1161/CIRCRESAHA.110.219493 CrossRefPubMedGoogle Scholar
  21. 21.
    Zhu D, Xie H, Wang X et al (2017) Catestatin-A novel predictor of left ventricular remodeling after acute myocardial infarction. Sci Rep.  https://doi.org/10.1038/srep44168 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    de Lucia C, Femminella GD, Gambino G et al (2014) Adrenal adrenoceptors in heart failure. Front Physiol 5:246.  https://doi.org/10.3389/fphys.2014.00246 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Jensen BC, O’Connell TD, Simpson PC (2011) Alpha-1-adrenergic receptors: targets for agonist drugs to treat heart failure. J Mol Cell Cardiol 51:518–528.  https://doi.org/10.1016/j.yjmcc.2010.11.014 CrossRefPubMedGoogle Scholar
  24. 24.
    Lymperopoulos A (2013) Physiology and pharmacology of the cardiovascular adrenergic system. Front Physiol 4:240.  https://doi.org/10.3389/fphys.2013.00240 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Pérez-Schindler J, Philp A, Hernandez-Cascales J (2013) Pathophysiological relevance of the cardiac β2-adrenergic receptor and its potential as a therapeutic target to improve cardiac function. Eur J Pharmacol 698:39–47.  https://doi.org/10.1016/j.ejphar.2012.11.001 CrossRefPubMedGoogle Scholar
  26. 26.
    Weber S, Meyer-Roxlau S, El-Armouche A (2016) Role of protein phosphatase inhibitor-1 in cardiac beta adrenergic pathway. J Mol Cell Cardiol 101:116–126.  https://doi.org/10.1016/j.yjmcc.2016.09.007 CrossRefPubMedGoogle Scholar
  27. 27.
    Gaede AH, Pilowsky PM (2012) Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM. Am J Physiol Regul Integr Comp Physiol 302:R365–R372.  https://doi.org/10.1152/ajpregu.00409.2011 CrossRefPubMedGoogle Scholar
  28. 28.
    Mazza R, Tota B, Gattuso A (2015) Cardio-vascular activity of catestatin: interlocking the puzzle pieces. Curr Med Chem 22:292–304CrossRefGoogle Scholar
  29. 29.
    Angelone T, Quintieri AM, Brar BK et al (2008) The antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modulator of cardiac inotropism and lusitropism. Endocrinology 149:4780–4793.  https://doi.org/10.1210/en.2008-0318 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Angelone T, Quintieri AM, Pasqua T et al (2012) Phosphodiesterase type-2 and NO-dependent S-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin. Am J Physiol Heart Circ Physiol 302:H431–H442.  https://doi.org/10.1152/ajpheart.00491.2011 CrossRefPubMedGoogle Scholar
  31. 31.
    Rodrigues JV, Gomes CM (2010) Enhanced superoxide and hydrogen peroxide detection in biological assays. Free Radic Biol Med 49:61–66.  https://doi.org/10.1016/j.freeradbiomed.2010.03.014 CrossRefPubMedGoogle Scholar
  32. 32.
    Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5:51–66.  https://doi.org/10.1038/nprot.2009.197 CrossRefPubMedGoogle Scholar
  33. 33.
    Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem FEBS 47:469–474CrossRefGoogle Scholar
  34. 34.
    Gupta MK, Neelakantan TV, Sanghamitra M et al (2006) An assessment of the role of reactive oxygen species and redox signaling in norepinephrine-induced apoptosis and hypertrophy of H9c2 cardiac myoblasts. Antioxid Redox Signal 8:1081–1093.  https://doi.org/10.1089/ars.2006.8.1081 CrossRefPubMedGoogle Scholar
  35. 35.
    Saleem N, Goswami SK (2017) Activation of adrenergic receptor in H9c2 cardiac myoblasts co-stimulates Nox2 and the derived ROS mediate the downstream responses. Mol Cell Biochem.  https://doi.org/10.1007/s11010-017-3088-8 CrossRefPubMedGoogle Scholar
  36. 36.
    Bassino E, Fornero S, Gallo MP et al (2015) Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential. PLoS ONE.  https://doi.org/10.1371/journal.pone.0119790 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Liao F, Zheng Y, Cai J et al (2015) Catestatin attenuates endoplasmic reticulum induced cell apoptosis by activation type 2 muscarinic acetylcholine receptor in cardiac ischemia/reperfusion. Sci Rep.  https://doi.org/10.1038/srep16590 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Dirkx E, da Costa Martins PA, De Windt LJ (2013) Regulation of fetal gene expression in heart failure. Biochim Biophys Acta 1832:2414–2424.  https://doi.org/10.1016/j.bbadis.2013.07.023 CrossRefPubMedGoogle Scholar
  39. 39.
    Kanaan GN, Harper ME (2017) Cellular redox dysfunction in the development of cardiovascular diseases. Biochim Biophys Acta.  https://doi.org/10.1016/j.bbagen.2017.07.027 CrossRefGoogle Scholar
  40. 40.
    Jindal E, Goswami SK (2011) In cardiac myoblasts, cellular redox regulates FosB and Fra-1 through multiple cis-regulatory modules. Free Radic Biol Med 51:1512–1521.  https://doi.org/10.1016/j.freeradbiomed.2011.07.008 CrossRefPubMedGoogle Scholar
  41. 41.
    Saleem N, Prasad A, Goswami SK (2018) Apocynin prevents isoproterenol-induced cardiac hypertrophy in rat. Mol Cell Biochem 445:79–88.  https://doi.org/10.1007/s11010-017-3253-0 CrossRefPubMedGoogle Scholar
  42. 42.
    Thakur A, Alam MJ, Ajayakumar MR et al (2015) Norepinephrine-induced apoptotic and hypertrophic responses in H9c2 cardiac myoblasts are characterized by different repertoire of reactive oxygen species generation. Redox Biol 5:243–252.  https://doi.org/10.1016/j.redox.2015.05.005 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wang Y, Branicky R, Noë A, Hekimi S (2018) Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol 217:1915–1928.  https://doi.org/10.1083/jcb.201708007 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Cabassi A, Binno SM, Tedeschi S et al (2014) Low serum ferroxidase I activity is associated with mortality in heart failure and related to both peroxynitrite-induced cysteine oxidation and tyrosine nitration of ceruloplasmin. Circ Res 114:1723–1732.  https://doi.org/10.1161/CIRCRESAHA.114.302849 CrossRefPubMedGoogle Scholar
  45. 45.
    Paulova H, Stracina T, Jarkovsky J et al (2013) Hydroxyl radicals’ production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart. Gen Physiol Biophys 32:221–228.  https://doi.org/10.4149/gpb_2013016 CrossRefPubMedGoogle Scholar
  46. 46.
    Sies H, Berndt C, Jones DP (2017) Oxidative Stress. Annu Rev Biochem 86:715–748.  https://doi.org/10.1146/annurev-biochem-061516-045037 CrossRefPubMedGoogle Scholar
  47. 47.
    Barančík M, Grešová L, Barteková M, Dovinová I (2016) Nrf2 as a key player of redox regulation in cardiovascular diseases. Physiol Res 65(Suppl 1):S1–S10PubMedGoogle Scholar
  48. 48.
    Gang C, Qiang C, Xiangli C et al (2015) Puerarin suppresses angiotensin II-induced cardiac hypertrophy by inhibiting NADPH oxidase activation and oxidative stress-triggered AP-1 signaling pathways. J Pharm Pharm Sci 18:235–248CrossRefGoogle Scholar
  49. 49.
    Hill C, Würfel A, Heger J et al (2013) Inhibition of AP-1 signaling by JDP2 overexpression protects cardiomyocytes against hypertrophy and apoptosis induction. Cardiovasc Res 99:121–128.  https://doi.org/10.1093/cvr/cvt094 CrossRefPubMedGoogle Scholar
  50. 50.
    Suzuki T, Yamamoto M (2017) Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress. J Biol Chem.  https://doi.org/10.1074/jbc.R117.800169 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Windak R, Müller J, Felley A et al (2013) The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. PLoS ONE 8:e73294.  https://doi.org/10.1371/journal.pone.0073294 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Selvaraj N, Budka JA, Ferris MW et al (2015) Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration. Mol Cell Biol 35:88–100.  https://doi.org/10.1128/MCB.00982-14 CrossRefPubMedGoogle Scholar
  53. 53.
    Li P, Spolski R, Liao W, Leonard WJ (2014) Complex interactions of transcription factors in mediating cytokine biology in T cells. Immunol Rev 261:141–156.  https://doi.org/10.1111/imr.12199 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Fujita T, Toya Y, Iwatsubo K et al (2001) Accumulation of molecules involved in alpha1-adrenergic signal within caveolae: caveolin expression and the development of cardiac hypertrophy. Cardiovasc Res 51:709–716CrossRefGoogle Scholar
  55. 55.
    Gesmundo I, Miragoli M, Carullo P et al (2017) Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure. Proc Natl Acad Sci USA 114:12033–12038.  https://doi.org/10.1073/pnas.1712612114 CrossRefPubMedGoogle Scholar
  56. 56.
    Ianoul A, Grant DD, Rouleau Y et al (2005) Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of cardiac myocytes. Nat Chem Biol 1:196–202.  https://doi.org/10.1038/nchembio726 CrossRefPubMedGoogle Scholar
  57. 57.
    Vyas FS, Nelson CP, Dickenson JM (2018) Role of transglutaminase 2 in A1 adenosine receptor- and β2-adrenoceptor-mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation-induced cell death in H9c2 cells. Eur J Pharmacol 819:144–160.  https://doi.org/10.1016/j.ejphar.2017.11.049 CrossRefPubMedGoogle Scholar
  58. 58.
    Crowley LC, Marfell BJ, Scott AP et al (2016) Dead cert: measuring cell death. Cold Spring Harb Protoc.  https://doi.org/10.1101/pdb.top070318 CrossRefPubMedGoogle Scholar
  59. 59.
    Barry SP, Davidson SM, Townsend PA (2008) Molecular regulation of cardiac hypertrophy. Int J Biochem Cell Biol 40:2023–2039.  https://doi.org/10.1016/j.biocel.2008.02.020 CrossRefPubMedGoogle Scholar
  60. 60.
    Fu Y, Xiao H, Zhang Y (2012) Beta-adrenoceptor signaling pathways mediate cardiac pathological remodeling. Front Biosci Elite Ed 4:1625–1637CrossRefGoogle Scholar
  61. 61.
    O’Connell TD, Jensen BC, Baker AJ, Simpson PC (2014) Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev 66:308–333.  https://doi.org/10.1124/pr.112.007203 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Manda G, Isvoranu G, Comanescu MV et al (2015) The redox biology network in cancer pathophysiology and therapeutics. Redox Biol 5:347–357.  https://doi.org/10.1016/j.redox.2015.06.014 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Spencer NY, Engelhardt JF (2014) The basic biology of redoxosomes in cytokine-mediated signal transduction and implications for disease-specific therapies. Biochemistry 53:1551–1564.  https://doi.org/10.1021/bi401719r CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Sam F, Kerstetter DL, Pimental DR et al (2005) Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium. J Card Fail 11:473–480.  https://doi.org/10.1016/j.cardfail.2005.01.007 CrossRefPubMedGoogle Scholar
  65. 65.
    Srivastava S, Chandrasekar B, Gu Y et al (2007) Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res 74:445–455.  https://doi.org/10.1016/j.cardiores.2007.02.016 CrossRefPubMedGoogle Scholar
  66. 66.
    Kiranmayi M, Chirasani VR, Allu PKR et al (2016) Catestatin Gly364Ser variant alters systemic blood pressure and the risk for hypertension in human populations via endothelial nitric oxide pathway. Hypertens Dallas Tex 68:334–347.  https://doi.org/10.1161/HYPERTENSIONAHA.116.06568 CrossRefGoogle Scholar
  67. 67.
    Sahu BS, Mohan J, Obbineni JM et al (2012) Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor. J Cell Sci 125:2323–2337.  https://doi.org/10.1242/jcs.103176 CrossRefPubMedGoogle Scholar
  68. 68.
    Schmidt SF, Madsen JG, Frafjord KO et al (2016) Integrative genomics outlines a biphasic glucose response and a ChREBP-RORgamma axis regulating proliferation in beta cells. Cell Rep 16:2359–2372.  https://doi.org/10.1016/j.celrep.2016.07.063 CrossRefPubMedGoogle Scholar
  69. 69.
    Zhang X, Meng J, Wang ZY (2012) A switch role of Src in the biphasic EGF signaling of ER-negative breast cancer cells. PLoS ONE 7:e41613.  https://doi.org/10.1371/journal.pone.0041613 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Kazanietz MG, Gutkind JS, Puyo A et al (1989) Further evidence of interaction between vasodilator beta 2- and vasoconstrictor alpha 2-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats. J Cardiovasc Pharmacol 14:874–880CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Translational Health Science and Technology InstituteNCR Biotech Science ClusterFridabadIndia
  2. 2.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  3. 3.Department of Biotechnology, Bhupat and Jyoti Mehta School of BiosciencesIndian Institute of Technology MadrasChennaiIndia

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