Abstract OBJECTIVE: To study the effects of erythropoietin (EPO) on cardiomyocyte apoptosis and endoplasmic reticulum stress (ERS)-related proteins, glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in neonatal rats with asphyxia. METHODS: A total of 120 newborn Sprague-Dawley rats (7 days old) were randomly divided into sham-operated (n=40), asphyxia (n=40) and EPO-treated asphyxia groups (n=40). A neonatal rat model of normobaric asphyxia was established in the asphyxia and EPO-treated asphyxia groups. The rats in the EPO-treated asphyxia group received intraperitoneal injection of recombinant human erythropoietin (500 U/mL) immediately after the model was established, while the other two groups received the same volume of normal saline (0.9%). Heart blood and myocardial tissue samples were collected from 8 rats in each group at 2, 6, 12, 24 or 48 hours after the model was established. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were measured; cardiomyocyte apoptosis was evaluated, and expression of myocardial GRP78 and CHOP was measured. RESULTS: Compared with the sham-operated and EPO-treated asphyxia groups, the asphyxia group had significantly increased serum CK and LDH levels, number of apoptotic cells, and expression of myocardial GRP78 and CHOP at each time point (P<0.01), and all the indices were significantly higher in the EPO-treated asphyxia group than in the sham-operated group (P<0.01). At 24 hours after asphyxia, the expression of myocardial CHOP was positively correlated with the myocardial apoptosis index (r=0.944, P<0.01). CONCLUSIONS: EPO exerts a protective effect on the myocardium of neonatal rats with hypoxic-ischemic injury by regulating ERS-related proteins GRP78 and CHOP and reducing cardiomyocyte apoptosis.
WAN Li-Jia,WU Xing-Heng. Effects of erythropoietin on cardiomyocyte apoptosis and endoplasmic reticulum stress-related proteins in neonatal rats with asphyxia[J]. CJCP, 2013, 15(10): 890-895.
WAN Li-Jia,WU Xing-Heng. Effects of erythropoietin on cardiomyocyte apoptosis and endoplasmic reticulum stress-related proteins in neonatal rats with asphyxia[J]. CJCP, 2013, 15(10): 890-895.
Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease[J]. Apoptosis, 2009, 14(4): 536-548.
[3]
Zhang K, Kaufman RJ. Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo[J]. Methods Enzymol, 2008, 442: 395-419.
[4]
Lee AS. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress[J]. Methods, 2005, 35(4): 373-381.
[5]
Faitova J, Krekac D, Hrstka R, Vojtesek B. Endoplasmic reticu-lum stress and apoptosis[J]. Cell Mol Biol Lett, 2006, 11(4): 488-505.
[6]
Chateauvieux S, Grigorakaki C, Morceau F, Dicato M, Diederich M. Erythropoietin, erythropoiesis and beyond[J]. Biochem Pharmacol, 2011, 82(10): 1291-1303.
[7]
Kumral A, Tuzun F, Oner MG, Genc S, Duman N, Ozkan H. Erythropoietin in neonatal brain protection: the past, the present and the future[J]. Brain Dev, 2011, 33(8): 632-643.
[8]
Ruifrok WP, de Boer RA, Westenbrink BD, van Veldhuisen DJ, van Gilst WH. Erythropoietin in cardiac disease: new features of an old drug[J]. Eur J Pharmacol, 2008, 585(2-3): 270-277.
[9]
Lu MJ, Chen YS, Huang HS, Ma MC. Erythropoietin alleviates post-ischemic injury of rat hearts by attenuating nitrosative stress[J]. Life Sci, 2012, 90(19-20): 776-784.
[10]
Kretz A, Happold CJ, Marticke JK, Isenmann S. Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation[J]. Mol Cell Neurosci, 2005, 29(4): 569-579.
[11]
Tang Z, Sun X, Huo G, Xie Y, Shi Q, Chen S, et al. Protective effects of erythropoietin on astrocytic swelling after oxygen-glucose deprivation and reoxygenation: mediation through AQP4 expression and MAPK pathway[J]. Neuropharmacology, 2013, 67: 8-15.
