Skip to main content
Log in

Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes

  • Short Communication
  • Published:
Apoptosis Aims and scope Submit manuscript


Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 μM (H2O2 group), propofol at 50 μM (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. White PF (2008) Propofol: its role in changing the practice of anesthesia. Anesthesiology 109(6):1132–1136

    Article  CAS  PubMed  Google Scholar 

  2. Jin YC, Kim W, Ha YM et al (2009) Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo. Vascul Pharmacol 50(1–2):71–77

    Article  CAS  PubMed  Google Scholar 

  3. Sun HY, Xue FS, Xu YC et al (2009) Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts. Chin Med J (Engl) 122(24):3048–3054

    CAS  Google Scholar 

  4. Shao H, Li J, Zhou Y et al (2008) Dose-dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin. Br J Pharmacol 153(8):1641–1649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Liu Q, Yao JY, Qian C et al (2012) Effects of propofol on ischemia-induced ventricular arrhythmias and mitochondrial ATP-sensitive potassium channels. Acta Pharmacol Sin 33(12):1495–1501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lee Y, Gustafsson AB (2009) Role of apoptosis in cardiovascular disease. Apoptosis 14(4):536–548

    Article  PubMed  Google Scholar 

  7. Whelan RS, Kaplinskiy V, Kitsis RN (2010) Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol 72:19–44

    Article  CAS  PubMed  Google Scholar 

  8. Addabbo F, Montagnani M, Goligorsky MS (2009) Mitochondria and reactive oxygen species. Hypertension 53(6):885–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13(3):363–373

    Article  CAS  PubMed  Google Scholar 

  10. Yao W, Cai H, Li X et al (2014) Endoplasmic reticulum stress links hepatitis C virus RNA replication to wild-type PGC-1alpha/liver-specific PGC-1alpha upregulation. J Virol 88(15):8361–8374

    Article  PubMed  PubMed Central  Google Scholar 

  11. Szegezdi E, Logue SE, Gorman AM et al (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7(9):880–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Groenendyk J, Agellon LB, Michalak M (2012) Coping with endoplasmic reticulum stress in the cardiovascular system. Annu Rev Physiol 75:49–67

    Article  PubMed  Google Scholar 

  13. Minamino T, Kitakaze M (2010) ER stress in cardiovascular disease. J Mol Cell Cardiol 48(6):1105–1110

    Article  CAS  PubMed  Google Scholar 

  14. Tirasophon W, Welihinda AA, Kaufman RJ (1998) A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev 12(12):1812–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nakagawa T, Zhu H, Morishima N et al (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403(6765):98–103

    Article  CAS  PubMed  Google Scholar 

  16. Palomer X, Capdevila-Busquets E, Botteri G et al (2014) PPARbeta/delta attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells. Int J Cardiol 174(1):110–118

    Article  PubMed  Google Scholar 

  17. Guo R, Liu W, Liu B et al (2015) SIRT1 suppresses cardiomyocyte apoptosis in diabetic cardiomyopathy: An insight into endoplasmic reticulum stress response mechanism. Int J Cardiol 191:36–45

    Article  PubMed  Google Scholar 

  18. Belaidi E, Thomas A, Bourdier G et al (2016) Endoplasmic reticulum stress as a novel inducer of hypoxia inducible factor-1 activity: its role in the susceptibility to myocardial ischemia-reperfusion induced by chronic intermittent hypoxia. Int J Cardiol 210:45–53

    Article  PubMed  Google Scholar 

  19. Wu H, Ye M, Yang J et al (2016) Modulating endoplasmic reticulum stress to alleviate myocardial ischemia and reperfusion injury from basic research to clinical practice: a long way to go. Int J Cardiol 223:630–631

    Article  PubMed  Google Scholar 

  20. Chai W, Zhang W, Jin Z et al (2012) Angiotensin II type I receptor agonistic autoantibody-induced apoptosis in neonatal rat cardiomyocytes is dependent on the generation of tumor necrosis factor-alpha. Acta Biochim Biophys Sin (Shanghai) 44(12):984–990

    Article  CAS  Google Scholar 

  21. Ichinose M, Yonemochi H, Sato T et al (2003) Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress. Am J Physiol Heart Circ Physiol 284(6):H2235–H2241

    Article  CAS  PubMed  Google Scholar 

  22. Liu XR, Tan XQ, Yang Y et al (2012) Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice. Acta Pharmacol Sin 33(1):19–26

    Article  PubMed  Google Scholar 

  23. Rajendran P, Nandakumar N, Rengarajan T et al (2014) Antioxidants and human diseases. Clin Chim Acta 436:332–347

    Article  CAS  PubMed  Google Scholar 

  24. von Harsdorf R, Li PF, Dietz R (1999) Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation 99(22):2934–2941

    Article  Google Scholar 

  25. Rodrigo R, Prieto JC, Castillo R (2013) Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n-3 fatty acids: molecular mechanisms and potential clinical applications. Clin Sci (Lond) 124(1):1–15

    Article  CAS  Google Scholar 

  26. Urao N, Ushio-Fukai M (2013) Redox regulation of stem/progenitor cells and bone marrow niche. Free Radic Biol Med 54:26–39

    Article  CAS  PubMed  Google Scholar 

  27. Burgoyne JR, Mongue-Din H, Eaton P et al (2012) Redox signaling in cardiac physiology and pathology. Circ Res 111(8):1091–1106

    Article  CAS  PubMed  Google Scholar 

  28. Fan TJ, Han LH, Cong RS et al (2005) Caspase family proteases and apoptosis. Acta Biochim Biophys Sin (Shanghai) 37(11):719–727

    Article  CAS  Google Scholar 

  29. Wang ZB, Liu YQ, Cui YF (2005) Pathways to caspase activation. Cell Biol Int 29(7):489–496

    Article  CAS  PubMed  Google Scholar 

  30. Kim B, Srivastava SK, Kim SH (2015) Caspase-9 as a therapeutic target for treating cancer. Expert Opin Ther Targets 19(1):113–127

    Article  CAS  PubMed  Google Scholar 

  31. Szegezdi E, Fitzgerald U, Samali A (2003) Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann N Y Acad Sci 1010:186–194

    Article  CAS  PubMed  Google Scholar 

  32. Gu Q, Wang JD, Xia HH et al (2005) Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer. Carcinogenesis 26(3):541–546

    Article  CAS  PubMed  Google Scholar 

  33. Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22(12):1577–1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Parra V, Eisner V, Chiong M et al (2008) Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovasc Res 77(2):387–397

    Article  CAS  PubMed  Google Scholar 

  35. Kaufman RJ (2002) Orchestrating the unfolded protein response in health and disease. J Clin Invest 110(10):1389–1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Goldenberg-Cohen N, Raiter A, Gaydar V et al (2012) Peptide-binding GRP78 protects neurons from hypoxia-induced apoptosis. Apoptosis 17(3):278–288

    Article  CAS  PubMed  Google Scholar 

  37. Li N, Zoubeidi A, Beraldi E et al (2012) GRP78 regulates clusterin stability, retrotranslocation and mitochondrial localization under ER stress in prostate cancer. Oncogene 32(15):1933–1942

    Article  PubMed  Google Scholar 

  38. Wu H, Ye M, Yang J et al (2015) Nicorandil protects the heart from ischemia/reperfusion injury by attenuating endoplasmic reticulum response-induced apoptosis through PI3K/Akt signaling pathway. Cell Physiol Biochem 35(6):2320–2332

    Article  CAS  PubMed  Google Scholar 

  39. Wang B, Shravah J, Luo H et al (2009) Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation. Biochem Biophys Res Commun 389(1):105–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references


The research was supported by the National Natural Science Fundation of China (81670310), and Southwest Medical University Scientific Research Fund (2014QN-003). Authors would like to thank Prof. Ji-Min Cao from Chinese Academy of Medical Sciences and Prof. Xitong Dang from the University of California, San Diego for their critical reading of the manuscript.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Xiao-Qiu Tan.

Ethics declarations

Conflict of interest


Additional information

Xue-Ru Liu, Lu Cao and Tao Li have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 2796 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, XR., Cao, L., Li, T. et al. Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes. Apoptosis 22, 639–646 (2017).

Download citation

  • Published:

  • Issue Date:

  • DOI: