Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes

Hong-liang Kong; Zhan-quan Li; Shu-mei Zhao; Long Yuan; Zhi-lin Miao; Ying Liu; Ru-ming Guan

doi:10.1007/s11655-014-1774-2

Your Location：

Home >

Browse articles >

Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes

OriginalPaper | Updated：2021-08-27

- Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes
- Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes
- 中国结合医学杂志（英文版） 2015年21卷第2期页码：139-146
- Affiliations：
  
  1. Cardiology Center, The People’s Hospital of Liaoning Province,Shenyang,China
  2. Shenyang Normal University,Shenyang,China
- Author bio：
- Funds：
  
  Supported by Liaoning Province Science and Technique Foundation of China (No. 201102107)
- DOI：10.1007/s11655-014-1774-2
  中图分类号：
- 纸质出版日期：2015，
  
  网络出版日期：2014-6-3，
Scan for full text
Kong, Hl., Li, Zq., Zhao, Sm. et al. Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes., Chin. J. Integr. Med. 21, 139–146 (2015). https://doi.org/10.1007/s11655-014-1774-2

Hong-liang Kong, Zhan-quan Li, Shu-mei Zhao, et al. Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes[J]. Chinese Journal of Integrative Medicine, 2015,21(2):139-146.
Kong, Hl., Li, Zq., Zhao, Sm. et al. Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes., Chin. J. Integr. Med. 21, 139–146 (2015). https://doi.org/10.1007/s11655-014-1774-2 DOI：

Hong-liang Kong, Zhan-quan Li, Shu-mei Zhao, et al. Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes[J]. Chinese Journal of Integrative Medicine, 2015,21(2):139-146. DOI： 10.1007/s11655-014-1774-2.

摘要

To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α (Hif-1α). Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group

a simple CoCl group

a simple Gs-Rb1 group

a CoCl and Gs-Rb1 hypoxia group

a CoCl and 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) group

a CoCl and YC-1 group and a Gs-Rb1 group

in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl

Gs-Rb1 and YC-1 was 500 μmol/L

200 μmol/L and 5 μmol/L

respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin

APJ and Hif-1α were assayed with immunocytochemistry

Western blot assays and reverse transcription polymerase chain reaction (RT-PCR). (1) The anti-apoptosis effect of Gs-Rb1 on hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred

which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α

which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ

including mRNA and protein)

a positive correlation between apelin (or APJ) protein and Hif-1a protein

in hypoxia cardiomyocytes. The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes

which was partly adjusted by Hif-1α.

Abstract

a simple CoCl group

a simple Gs-Rb1 group

a CoCl and Gs-Rb1 hypoxia group

a CoCl and 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) group

a CoCl and YC-1 group and a Gs-Rb1 group

in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl

Gs-Rb1 and YC-1 was 500 μmol/L

200 μmol/L and 5 μmol/L

respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin

APJ and Hif-1α were assayed with immunocytochemistry

which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α

which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ

including mRNA and protein)

a positive correlation between apelin (or APJ) protein and Hif-1a protein

in hypoxia cardiomyocytes. The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes

which was partly adjusted by Hif-1α.

关键词

ginsenosides-Rb1cardiomyocyteshypoxiaapelinAPJhypoxia-induced factor 1α

Keywords

ginsenosides-Rb1cardiomyocyteshypoxiaapelinAPJhypoxia-induced factor 1α

references

Liu YF, Liu SW, Liu ZX. Effects of ginsenoside Rb1 on blood vessel regeneration after ischemia and reperfusion in rats. Chin J Histochem Cytochem (Chin) 2008;17:39–44.

Zeng HS, Liu ZX. Influence of ginsenoside Re on cardiomyocyte apoptosis and Fas expression after acute ischemia-reperfusion in rats. J Huazhong Univ Sci Tech (Health Sci, Chin) 2004;33:286–288.

Guan L, Li WZ, Liu ZX. Effect of ginsenoside-Rb1 on cardiomyocyte apoptosis after ischemia and reperfusion in rats. J Huazhong Univ Sci Technol (Med Sci, Chin) 2002;22:212–215.

Liu ZX, Liu XC. Effect of ginsenoside Rb1 and Re on cardiomyocyte apoptosis after ischemia and reperfusion in rats. Chin J Histochem Cytochem (Chin) 2002;11:374–377,506.

Kong HL, Wang JP, Li ZQ, Zhao SM, Dong J, Zhang WW. Anti-hypoxic effect of ginsenoside Rb1 on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo. Acta Pharmacol Sin (Chin) 2009;30:396–403.

Kong HL, Li ZQ, Zhao YJ, Zhao SM, Zhu L, Li T, et al. Ginsenoside Rb1 protects cardiomyocytes against CoCl2-induced apoptosis in neonatal rats by inhibiting mitochondria permeability transition pore opening. Acta Pharmacol Sin (Chin) 2010;31:687–695.

Kleinz MJ, Davenport AP. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 2004;118:119–125.

Kleinz MJ, Skepper JN, Davenport AP. Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Regul Pept 2005;126:233–240.

Chen MM, Ashley EA, Deng DX, Tsalenko A, Deng A, Tabibiazar R, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation 2003;108:1432–1439.

Barnes G, Japp AG, Newby DE. Translational promise of the apelin-APJ system. Heart 2010;96:1011–1016.

Pitkin SL, Maguire JJ, Kuc RE, Davenport AP. Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br J Pharmacol 2010;160:1785–1795.

Chandrasekaran B, Dar O, McDonagh T. The role of apelin in cardiovascular function and heart failure. Eur J Heart Fail 2008;10:725–732.

Quazi R, Palaniswamy C, Frishman WH. The emerging role of apelin in cardiovascular disease and health. Cardiol Rev 2009;17:283–286.

Ronkainen VP, Ronkainen JJ, Hänninen SL, Leskinen H, Ruas JL, Pereira T, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J 2007;21:1821–1830.

Han S, Wang G, Qi X, Lee HM, Englander EW, Greeley GH Jr. A possible role for hypoxia-induced apelin expression in enteric cell proliferation. Am J Physiol Regul Integr Comp Physiol 2008;294:R1832–R1839.

Glassford AJ, Yue P, Sheikh AY, Chun HJ, Zarafshar S, Chan DA, et al. HIF-1 regulates hypoxia- and insulininduced expression of apelin in adipocytes. Am J Physiol Endocrinol Metab 2007;293:E1590–E1596.

Zhang Z, Yu B, Tao GZ. Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation. Chin Med J 2009;122:2360–2365.

Zeng XJ, Zhang LK, Wang HX, Lu LQ, Ma LQ, Tang CS. Apelin protects heart against ischemia/reperfusion injury in rat. Peptides 2009;30:1144–1152.

Simpkin JC, Yellon DM, Davidson SM, Lim SY, Wynne AM, Smith CC. Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemia-reperfusion injury. Basic Res Cardiol 2007;102:518–528.

Lee S, Chanoit G, McIntosh R, Zvara DA, Xu Z. Molecular mechanism underlying Akt activation in zinc-induced cardioprotection. Am J Physiol Heart Circ Physiol 2009;297:H569–H575.

Miyamoto S, Murphy AN, Brown JH. Akt mediated mitochondrial protection in the heart: metabolic and survival pathways to the rescue. J Bioenerg Biomembr 2009;41:169–180.

Yao Y, Li L, Li L, Gao C, Shi C. Sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia reperfusion injury by activation of pro-survival kinases and inhibition of mitochondrial permeability transition pore opening upon reperfusion. Biol Pharm Bull 2009;32:1854–1861.

Juhaszova M, Zorov DB, Yaniv Y, Nuss HB, Wang S, Sollott SJ. Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res 2009;104:1240–1252.

Miura T, Miki T. GSK-3beta, a therapeutic target for cardiomyocyte protection. Circ J 2009;73:1184–1192.

Petrosillo G, Colantuono G, Moro N, Ruggiero FM, Tiravanti E, Di Venosa N, et al. Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. Am J Physiol Heart Circ Physiol 2009;297:H1487–H1493.

Yue P, Jin H, Xu S, Aillaud M, Deng AC, Azuma J, et al. Apelin decreases lipolysis via G(q), G(i), and AMPKdependent mechanisms. Endocrinology 2011;152:59–68.

Yue P, Jin H, Aillaud M, Deng AC, Azuma J, Asagami T, et al. Apelin is necessary for the maintenance of insulin sensitivity. Am J Physiol Endocrinol Metab 2010;298:E59–E67.

Masri B, Lahlou H, Mazarguil H, Knibiehler B, Audigier Y. Apelin (65–77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein. Biochem Biophys Res Commun 2002;290:539–545.

Kleinz MJ, Baxter GF. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept 2008;146:271–277.

Zhu W, Zou Y, Aikawa R, Harada K, Kudoh S, Uozumi H, et al. MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes. Circulation 1999;100:2100–2107.

Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, et al. Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res 2000;86:692–699.

Wenger RH. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J 2002;16:1151–1162.

Zhou YF, Zheng XW, Zhang GH, Zong ZH, Qi GX. The effect of hypoxia-inducible factor 1-alpha on hypoxiainduced apoptosis in primary neonatal rat ventricular myocytes. Cardiovascular J Africa 2010;21:37–41.

Keränen MA, Nykänen AI, Krebs R, Pajusola K, Tuuminen R, Alitalo K, et al. Cardiomyocyte-targeted Hif-1alpha gene therapy inhibits cardiomyocyte apoptosis and cardiac allograft vasculopathy in the rat. J Heart Lung Transplant 2010;29:1058–1066.

Date T, Mochizuki S, Belanger AJ, Yamakawa M, Luo Z, Vincent KA, et al. Expression of constitutively stable hybrid hypoxia-inducible factor-1alpha protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury. Am J Physiol Cell Physiol 2005;288:C314–C320.

Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 1995;92:5510–5514.

Sun HL, Liu YN, Huang YT, Pan SL, Huang DY, Guh JH, et al. YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia. Oncogene 2007;26:3941–3951.

Kim HL, Yeo EJ, Chun YS, Park JW. A domain responsible for Hif-1α degradation by YC-1, a novel anticancer agent. Int J Oncol 2006;29:255–260.

Lau CK, Yang ZF, Lam CT, Tam KH, Poon RT, Fan ST. Suppression of hypoxia inducible factor-1α (Hif-1α) by YC-1 is dependent on murine double minute 2 (Mdm2). Biochem Biophys Res Commun 2006;348:1443–1448.

FULL TEXT LINK

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway

Effect of Yifei Huoxue Granule (益肺活血颗粒) on the proliferation of rat pulmonary artery smooth muscle cells upon exposure to chronic hypoxic conditions in vitro

Salvianolic acid B inhibits the TLR4-NFκB-TNFα pathway and attenuates neonatal rat cardiomyocyte injury induced by lipopolysaccharide

Beneficial effect of HHI-I (活血化瘀注射液I号) on cerebral microcirculation, blood-brain barrier in rats and anti-hypoxic activity in mice

Effect of panax notoginseng saponins injection on the p38MAPK pathway in lung tissue in a rat model of hypoxic pulmonary hypertension