Calcitonin gene-related peptide affects cardiomyocyte apoptosis of neonatal rats induced by oxidized low-density lipoprotein and hypoxia/reoxygenation

doi:10.3969/j.issn.2095-4344.2014.11.020

Abstract

Abstract:

BACKGROUND: Previous studies have shown that calcitonin gene-related peptide can be released from cardiac sensory afferent terminals following coronary artery occlusion in rats, indicating the involvement of calcitonin gene-related peptide during pathological process of acute myocardial ischemia.

OBJECTIVE: To investigate the effect of calcitonin gene-related peptide on neonatal rat cardiomyocytes apoptosis induced by oxidized low-density lipoprotein and hypoxia/reoxygenation.

METHODS: Twenty wells of primary cultured neonatal rat myocardial cells were randomly divided into five groups: normal control group, oxidized low-density lipoprotein group, oxidized low-density lipoprotein hypoxia/reoxygenation group, calcitonin gene-related peptide group and calcitonin gene-related peptide_8-37 group. The cells in the last four groups were incubated with oxidized low-density lipoprotein for 24 hours before establishing the myocardial hypoxia/reoxygenation model. At 30 minutes prior to hypoxia/reoxygenation, 10^-8 mol/L calcitonin gene-related peptide were added into the culture fluid in calcitonin gene-related peptide group; 10^-7 mol/L competitive antagonist calcitonin gene-related peptide_8-37 of calcitonin gene-related peptide-1 receptor were added at 30 minutes before calcitonin gene-related peptide administration in calcitonin gene-related peptide_8-37 group. Myocardial apoptotic rate and caspase-3 activity were detected respectively.

RESULTS AND CONCLUSION: Calcitonin gene-related peptide could significantly attenuate apoptosis of neonatal rat myocardial cells through inhibiting the caspase-3 activation induced by oxidized low-density lipoprotein and hypoxia/reoxygenation. And this effect could be partially reversed by competitive antagonist calcitonin gene-related peptide_8-37 of calcitonin gene-related peptide 1 receptor, indicating that calcitonin gene-related peptide has anti-apoptotic effect in combination with the calcitonin gene-related peptide 1 receptor to inhibit cardiomyocyte apoptosis in neonatal rats induced by oxidized low-density lipoprotein and hypoxia/reoxygenation.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: calcitonin gene-related peptide, apoptosis, myocytes, cardiac, anoxia

CLC Number:

R318

Yue Wei, Zhu Guo-bin, Du Qiu-xiang, Guo Zheng. Calcitonin gene-related peptide affects cardiomyocyte apoptosis of neonatal rats induced by oxidized low-density lipoprotein and hypoxia/reoxygenation[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(11): 1761-1764.

Figures/Tables 2

References

[1] Saraste A, Pulkki K, Kallajoki M,et al.Apoptosis in human acute myocardial infarction.Circulation. 1997;95(2):320-323.

[2] 张建文,郭政.吗啡预先给药对急性心肌缺血大鼠心肌P物质和降钙素基因相关肽的影响[J].中华麻醉学杂志, 2006,26(10): 911-914.

[3] Brady NR, Hamacher-Brady A, Gottlieb RA.Proapoptotic BCL-2 family members and mitochondrial dysfunction during ischemia/reperfusion injury, a study employing cardiac HL-1 cells and GFP biosensors.Biochim Biophys Acta. 2006;1757 (5-6):667-678.

[4] Haunstetter A, Izumo S.Apoptosis: basic mechanisms and implications for cardiovascular disease.Circ Res. 1998;82(11): 1111-1129.

[5] Kita T, Kume N, Minami M,et al.Role of oxidized LDL in atherosclerosis.Ann N Y Acad Sci. 2001;947:199-205; discussion 205-206.

[6] Ehara S, Ueda M, Naruko T, et al.Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.Circulation. 2001; 103(15):1955-1960.

[7] Ekmekcioglu C, Mehrabi MR, Glogar HD,et al.Oxidized low-density lipoprotein is localized in the ventricles of hearts from patients with coronary heart disease.Int J Clin Lab Res. 2000;30(3):133-140.

[8] Iwai-Kanai E, Hasegawa K, Sawamura T,et al.Activation of lectin-like oxidized low-density lipoprotein receptor-1 induces apoptosis in cultured neonatal rat cardiac myocytes.Circulation. 2001;104(24):2948-2954.

[9] Guo J, Li HZ, Zhang WH, et al.Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia-reperfusion.Clin Exp Pharmacol Physiol. 2010; 37(3):e128-135.

[10] Hoover DB, Chang Y, Hancock JC,et al.Actions of tachykinins within the heart and their relevance to cardiovascular disease.Jpn J Pharmacol. 2000;84(4):367-373.

[11] 商立军,臧益民,王春梅,等.降钙素基因相关肽对心肌细胞缺血缺氧状态下胞内钙的影响[J].第四军医大学学报, 2000,21(4): 903-905.

[12] Wu DM, van Zwieten PA, Doods HN.Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats.Acta Pharmacol Sin. 2001; 22(7):588-594.