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Noscapine protects the H9c2 cardiomyocytes of rats against oxygen–glucose deprivation/reperfusion injury

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Abstract

Noscapine is an antitumor alkaloid derived from Papaver somniferum plants. Our previous study has demonstrated that exposure of noscapine on primary murine fetal cortical neurons exposed to oxygen–glucose deprivation/reperfusion (OGD/R) has neuroprotective effects. In current study, the effects of noscapine on cardiomyocytes (H9c2 cells) damage caused by 120 minutes (min) of OGD/R were evaluated and we determined whether the addition of BD1047, sigma-one receptor antagonist, prevents the protective effects of noscapine in H9c2 cells through the production of nitric oxide (NO) and apoptosis. To initiate OGD, H9c2 cells was transferred to glucose-free DMEM, and placed in a humidified incubation chamber. Cell viability was assessed with noscapine (1–5 μM) in the presence or absence of BD1047, 24 hours (h) after OGD/R. Cell viability, NO production and apoptosis ratio were evaluated by the MTT assay, the Griess method and the quantitative real-time PCR. Noscapine considerably improved the survival of H9c2 cells compared to OGD/R. Also, noscapine was extremely capable of reducing the concentrations of NO and Bax/Bcl-2 ratio expression. While the BD1047 administration alone diminished cell viability and increased the Bax/Bcl-2 ratio and NO levels. The addition of noscapine in the presence of BD1047 did not increase the cell viability relative to noscapine alone. Noscapine exerted cardioprotective effects exposed to OGD/R-induced injury in H9c2 cells, at least partly via attenuation of NO production and Bax/Bcl-2 ratio, which indicates that the sigma-one receptor activation is involved in the protection by noscapine of H9c2 cells injured by OGD/R.

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References

  1. Li Y-Y, **ang Y, Zhang S et al (2017) Thioredoxin-2 protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy and apoptosis in H9c2 cardiomyocytes. Am J Transl Res 9(3):1471–1482

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Zheng K, Sheng Z, Li Y et al (2014) Salidroside inhibits oxygen glucose deprivation (ogd)/re-oxygenation-induced h9c2 cell necrosis through activating of akt–nrf2 signaling. Biochem Biophys Res Commun 451(1):79–85

    CAS  PubMed  Google Scholar 

  3. Kalogeris T, Baines CP, Krenz M et al (2016) Ischemia/Reperfusion. Compr Physiol, Hoboken

    Google Scholar 

  4. Sun N, Yang L, Zhang Q et al (2018) Pioglitazone alleviates oxygen and glucose deprivation-induced injury by up-regulation of miR-454 in H9c2 cells. IJBMS 21(10):1050

    PubMed  PubMed Central  Google Scholar 

  5. Tavakoli-Far B, Rahbar-Roshandel N, Rahimi-Moghaddam P et al (2009) Neuroprotective effects of mebudipine and dibudipine on cerebral oxygen–glucose deprivation/reperfusion injury. Eur J Pharmacol 610(1–3):12–17

    CAS  PubMed  Google Scholar 

  6. Vahabzadeh G, Rahbar-Roshandel N, Ebrahimi S-A et al (2015) Neuroprotective effect of noscapine on cerebral oxygen–glucose deprivation injury. Pharmacol Rep 67(2):281–288

    CAS  PubMed  Google Scholar 

  7. Huang X, Zuo L, Lv Y et al (2016) Asiatic acid attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β/HIF-1α signaling in rat H9c2 cardiomyocytes. Molecules 21(9):1248

    PubMed Central  Google Scholar 

  8. Zhao L, Zhuang J, Wang Y et al (2019) Propofol ameliorates H9c2 cells apoptosis induced by oxygen glucose deprivation and reperfusion injury via inhibiting high levels of mitochondrial fusion and fission. Front Pharmacol 10:61

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Dumont M, Lemaire S (1991) Interaction of 1, 3-di (2-[5-3H] tolyl) guanidine with σ2 binding sites in rat heart membrane preparations. Eur J Pharmacol 209(3):245–248

    CAS  PubMed  Google Scholar 

  10. Novakova M, Ela C, Barg J et al (1995) Inotropic action of σ receptor ligands in isolated cardiac myocytes from adult rats. Eur J Pharmacol 286(1):19–30

    CAS  PubMed  Google Scholar 

  11. Gao Q-J, Yang B, Chen J et al (2018) Sigma-1 receptor stimulation with PRE-084 ameliorates myocardial ischemia-reperfusion injury in rats. Chin Med J 131(5):539

    PubMed  PubMed Central  Google Scholar 

  12. Maurice T, Su T-P (2009) The pharmacology of sigma-1 receptors. Pharmacol Ther 124(2):195–206

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Stracina T, Novakova M (2018) Cardiac sigma receptors-an update. Physiol Res 67(4):5561–5576

    Google Scholar 

  14. Stracina T, Slaninova I, Polanska H et al (2015) Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts. Tohoko j Eex Med 236(3):199–207

    CAS  Google Scholar 

  15. Zhang H, Cuevas J (2005) σ Receptor activation blocks potassium channels and depresses neuroexcitability in rat intracardiac neurons. J Pharmacol Exp Ther 313(3):1387–1396

    CAS  PubMed  Google Scholar 

  16. Altinoz MA, Topcu G, Hacimuftuoglu A et al (2019) Noscapine, a non-addictive opioid and microtubule-inhibitor in potential treatment of glioblastoma. Neurochem Res 44(8):1–11

    Google Scholar 

  17. Vahabzadeh G, Ebrahimi S-A, Rahbar-Roshandel N et al (2016) The effect of noscapine on oxygen-glucose deprivation on primary murine cortical neurons in high glucose condition. IJPR 15(2):501

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Khanmoradi M, Mard SA, Aboutaleb N et al (2014) The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat. IJBMS 17(4):244

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Cao A, Li X (2019) Bilobalide protects H9c2 cell from oxygen-glucose-deprivation-caused damage through upregulation of miR-27a. Artif Cells Blood Substit Biotechnol 47(1):2980–2988

    CAS  Google Scholar 

  20. Liu J, Sui H, Zhao J et al (2017) Osmotin protects H9c2 cells from simulated ischemia-reperfusion injury through AdipoR1/PI3K/AKT signaling pathway. Front Psychol 8:611

    Google Scholar 

  21. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–408

    CAS  PubMed  Google Scholar 

  22. **g L, Li Q, He L et al (2017) Protective effect of tempol against hypoxia-induced oxidative stress and apoptosis in H9c2 cells. Med Sci Monit Basic Res 23:159

    PubMed  PubMed Central  Google Scholar 

  23. Li W, Li Y, Sun R et al (2017) Dual character of flavonoids in attenuating and aggravating ischemia-reperfusion-induced myocardial injury. Exp Ther Med 14(2):1307–1314

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu J, Yang S, Zhang X et al (2016) Isoflurane reduces oxygen-glucose deprivation-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes. Am J Transl Res 8(6):2597

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Abdullah CS, Alam S, Aishwarya R et al (2018) Cardiac dysfunction in the sigma 1 receptor knockout mouse associated with impaired mitochondrial dynamics and bioenergetics. J Am Heart Assoc 7(20):e009775

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rousseaux CG, Greene SF (2016) Sigma receptors [σ Rs]: biology in normal and diseased states. J Recept Signal Transduct 36(4):327–388

    CAS  Google Scholar 

  27. Novakova M, Bruderova V, Sulova Z et al (2007) Modulation of expression of the sigma receptors in the heart of rat and mouse in normal and pathological conditions. Gen Physiol Biophys 26(2):110–117

    CAS  PubMed  Google Scholar 

  28. Novakova M, Sedlakova B, Sirova M et al (2010) Haloperidol increases expression of the inositol 1, 4, 5-trisphosphate receptors in rat cardiac atria, but not in ventricles. Gen Physiol Biophys 29(4):381

    CAS  PubMed  Google Scholar 

  29. Kamei J, Iwamoto Y, Misawa M et al (1993) Effects of rimcazole, a specific antagonist of σ sites, on the antitussive effects of non-narcotic antitussive drugs. Eur J Pharmacol 242(2):209–211

    CAS  PubMed  Google Scholar 

  30. Vahabzadeh G, Rahbar-Roshandel N, Ebrahimi S-A (2020) Noscapine modulates neuronal response to oxygen-glucose deprivation/reperfusion injury via activation of sigma-1 receptor in primary cortical cultures. IJPR 19(1):331–342. https://doi.org/10.22037/ijpr.2019.112317.13683

    Article  PubMed  PubMed Central  Google Scholar 

  31. Schulz R, Kelm M, Heusch G (2004) Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res 61(3):402–413

    CAS  PubMed  Google Scholar 

  32. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837

    PubMed  Google Scholar 

  33. Andrew PJ, Mayer B (1999) Enzymatic function of nitric oxide synthases. Cardiovasc Res 43(3):521–531

    CAS  PubMed  Google Scholar 

  34. Taimor G, Hofstaetter B, Piper HM (2000) Apoptosis induction by nitric oxide in adult cardiomyocytes via cGMP-signaling and its impairment after simulated ischemia. Cardiovasc Res 45(3):588–594

    CAS  PubMed  Google Scholar 

  35. Pacher P, Beckman SJ, Liaudet L (2007) Peroxynitrite in Health and Disease, ed. Physiol Rev 87(1):315–424

    CAS  PubMed  Google Scholar 

  36. Wang P, Chen H, Qin H et al (1996) Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury. J Biol Chem 271(46):29223–29230

    CAS  PubMed  Google Scholar 

  37. Vagnerova K, Hurn PD, Bhardwaj A et al (2006) Sigma 1 receptor agonists act as neuroprotective drugs through inhibition of inducible nitric oxide synthase. Anesth Analg 103(2):430–434

    CAS  PubMed  Google Scholar 

  38. Bhardwaj A, Sawada M, London ED et al (1998) Potent ~ 1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine modulates basal and N-methyl-D-aspartate-evoked nitric oxide production in vivo. Stroke 29:2404–2410

    CAS  PubMed  Google Scholar 

  39. Zughaier S, Karna P, Stephens D et al (2010) Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs. PLoS ONE 5(2):e9165

    PubMed  PubMed Central  Google Scholar 

  40. Hofstaetter B, Taimor G, Inserte J et al (2002) Inhibition of apoptotic responses after ischemic stress in isolated hearts and cardiomyocytes. Basic Res Cardiol 97(6):479–488

    CAS  PubMed  Google Scholar 

  41. Ekhterae D, Lin Z, Lundberg MS et al (1999) ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells. Circ Res 85(12):e70–e77

    CAS  PubMed  Google Scholar 

  42. Wu W-Y, Wang W-Y, Ma Y-L et al (2013) Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway. Br J Pharmacol 169(5):1058–1071

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Yang C, Li B, Liu Y et al (2019) Ginsenoside Rb1 protects cardiomyocytes from oxygen-glucose deprivation injuries by targeting microRNA-21. Exp Ther Med 17(5):3709–3716

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang L, Zhang Y, Wan H et al (2017) Glycyrrhetinic acid protects H9c2 cells from oxygen glucose deprivation-induced injury through the PI3K/AKt signaling pathway. J Nat Med 71(1):27–35

    PubMed  Google Scholar 

  45. Yang S, Bhardwaj A, Cheng J et al (2007) Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2. Anesth Analg 104(5):1179

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgement

The authors thank Dr. Mansour Torab for skillful technical assistance.

Funding

This work was supported by Iran University of Medical Sciences (IR.IUMS.REC1393.25042).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Gelareh Vahabzadeh, Hamidreza Soltani, Majid Jafari-Sabet & Ashrafolsadat Moazam

  2. Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran

    Mahmood Barati

  3. Cellular and Molecular Research Center, Iran University of Medical Science, Tehran, Iran

    Gelareh Vahabzadeh & Fereshteh Golab

  4. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Majid Jafari-Sabet & Sepideh Safari

  5. Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Science, Islamic Azad University, Tehran, Iran

    Hananeh Mohamadrezaei

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  1. Gelareh Vahabzadeh
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Correspondence to Gelareh Vahabzadeh.

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All the authors declared that they have no conflict of interest. No human or animal was used in this study.

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Vahabzadeh, G., Soltani, H., Barati, M. et al. Noscapine protects the H9c2 cardiomyocytes of rats against oxygen–glucose deprivation/reperfusion injury. Mol Biol Rep 47, 5711–5719 (2020). https://doi.org/10.1007/s11033-020-05549-6

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