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Medical Molecular Morphology

, Volume 51, Issue 2, pp 96–101 | Cite as

Creatine phosphate disodium salt protects against Dox-induced cardiotoxicity by increasing calumenin

  • Yu Wang
  • Ying Sun
  • Xin Guo
  • Yao Fu
  • Jie Long
  • Cheng-Xi Wei
  • Ming Zhao
Original Paper

Abstract

Inhibiting endoplasmic reticulum stress (ERS)-induced apoptosis may be a new therapeutic target in cardiovascular diseases. Creatine phosphate disodium salt (CP) has been reported to have cardiovascular protective effect, but its effects on ERS are unknown. The aim of this study was to identify the mechanism by which CP exerts its cardioprotection in doxorubicin (Dox)-induced cardiomyocytes injury. In our study, neonatal rats cardiomyocytes (NRC) was randomly divided into control group, model group, and treatment group. The cell viability and apoptosis were detected. grp78, grp94, and calumenin of the each group were monitored. To investigate the role of calumenin, Dox-induced ERS was compared in control and down-regulated calumenin cardiomyocytes. Our results showed that CP decreased Dox-induced apoptosis and relieved ERS. We found calumenin increased in Dox-induced apoptosis with CP. ERS effector C/EBP homologous protein was down-regulated by CP and it was influenced by calumenin. CP could protect NRC by inhibiting ERS, this mechanisms may be associated with its increasing of calumenin.

Keywords

Creatine phosphate disodium salt Doxorubicin Endoplasmic reticulum stress 

Notes

Funding

This work was supported by the National Natural Science Foundation of China (no. 81360587), the Natural Science Foundation of Inner Mongolia (no. 2016BS0806), Dr. Science Research Startup Funds of Inner Mongolia University for Nationalities (no. BS345), and the Mongolian medicine systems biology science and technology innovation team plan of Inner Mongolia.

References

  1. 1.
    Xin W, Li X, Lu X, Niu K, Cai J (2011) Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med 27:503–509PubMedGoogle Scholar
  2. 2.
    Dicks N, Gutierrez K, Michalak M, Bordignon V, Agellon LB (2015) Endoplasmic reticulum stress, genome damage, and cancer. Front Oncol 5:11CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Saito S, Furuno A, Sakurai J, Sakamoto A, Park HR, Shin-Ya K, Tsuruo T, Tomida A (2009) Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation. Cancer Res 69:4225–4234CrossRefPubMedGoogle Scholar
  4. 4.
    Zhang Q, Li H, Wang S, Liu M, Feng Y, Wang X (2013) Icariin protects rat cardiac H9c2 cells from apoptosis by inhibiting endoplasmic reticulum stress. Int J Mol Sci 14:17845–17860CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Isodono K, Takahashi T, Imoto H, Nakanishi N, Ogata T, Asada S, Adachi A, Ueyama T, Oh H, Matsubara H (2010) PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes. PLoS One 5:e9746CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gao X, Fu L, Xiao M, Xu C, Sun L, Zhang T, Zheng F, Mei C (2012) The nephroprotective effect of tauroursodeoxycholic acid on ischaemia/reperfusion-induced acute kidney injury by inhibiting endoplasmic reticulum stress. Basic Clin Pharmacol Toxicol 111:14–23PubMedGoogle Scholar
  7. 7.
    Okada T, Yoshida H, Akazawa R, Negishi M, Mori K (2002) Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J 366(Pt 2):585–594CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lai E, Teodoro T, Volchuk A (2007) Endoplasmic reticulum stress: signaling the unfolded protein response. Physiology (Bethesda) 22:193–201Google Scholar
  9. 9.
    Feng H, Chen L, Wang Q, Shen B, Liu L, Zheng P, Xu S, Liu X, Chen J, Teng J (2013) Calumenin-15 facilitates filopodia formation by promoting TGF-β superfamily cytokine GDF-15 transcription. Cell Death Dis 4:e870CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Yu W, Liying X, Xiaoxue C, Yilin W, Shaoqing C, Chengxi W, Ming Z (2017) Ibutilide treatment protects against ER stress induced apoptosis by regulating calumenin expression in tunicamycin treated cardiomyocytes. PLos one 12:e0173469CrossRefGoogle Scholar
  11. 11.
    Jiang Y, Sun C, Ding X, Yuan D, Chen K, Gao B, Chen Y, Sun A (2012) Simultaneous determination of adenine nucleotides, creatine phosphate and creatine in rat liver by high performance liquid chromatography–electrospray ionization-tandem mass spectrometry. J Pharm Biomed Anal 66:258–263CrossRefPubMedGoogle Scholar
  12. 12.
    Nakae I, Mitsunami K, Omura T, Yabe T, Tsutamoto T, Matsuo S, Takahashi M, Morikawa S, Inubushi T, Nakamura Y, Kinoshita M, Horie M (2003) Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy. J Am Coll Cardiol 42:1587–1593CrossRefPubMedGoogle Scholar
  13. 13.
    Xie Z, Wei L, Yang Q, Yang M, Pan H, Liu H (2016) A stability-indicating HPLC method for simultaneous determination of creatine phosphate sodium and its related substances in pharmaceutical formulation. Iran J Pharm Res 15:119–130PubMedPubMedCentralGoogle Scholar
  14. 14.
    Miles MF, Wilke N, Elliot M, Tanner W, Shah S (1994) Ethanol-responsive genes in neural cells include the 78-kilodalton glucose-regulated protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) molecular chaperones. Mol Pharmacol 46:873–879PubMedGoogle Scholar
  15. 15.
    Jia Y, Jucius TJ, Cook SA, Ackerman S (2015) Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration. J Neurosci 35:3001–3009CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sahoo SK, Kim T, Kang GB, Lee JG, Eom SH, Kim DH (2009) Characterization of calumenin-SERCA2 interaction in mouse cardiac sarcoplasmic reticulum. J Biol Chem 284:31109–31121CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Aune Westergaard Hansen G, Ludvigsen M, Jacobsen C, Cangemi C, Melholt Rasmussen L, Vorum H, Honoré B (2015) Correction: fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75 interact with the CREC proteins, calumenin and reticulocalbin. PLoS One 10:e0139293CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wang Q, Shen B, Chen L, Zheng P, Feng H, Hao Q, Liu X, Liu L, Xu S, Chen J, Teng J (2015) Extracellular calumenin suppresses ERK1/2 signaling and cell migration by protecting fibulin-1 from MMP-13-mediated proteolysis. Oncogene 34:1006–1018CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Clinical Molecular Morphology 2017

Authors and Affiliations

  1. 1.Inner Mongolia University for the NationalitiesTongliaoPeople’s Republic of China
  2. 2.Affiliated Hospital of Inner Mongolia University for NationalitiesTongliaoPeople’s Republic of China
  3. 3.Radiation CenterBeijing Shijitan Hospital of Capital Medical UniversityBeijingPeople’s Republic of China
  4. 4.Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular SystemTongliaoPeople’s Republic of China

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