The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin

被引:101
作者
Wang, XY
Zhu, CL
Wang, XH
Gerwien, JG
Schrattenholz, A
Sandberg, M
Leist, M
Blomgren, K
机构
[1] Gothenburg Univ, Dept Physiol, Perinatal Ctr, SE-40530 Gothenburg, Sweden
[2] Zhengzhou Univ, Affiliated Hosp 3, Dept Pediat, Zhengzhou, Peoples R China
[3] H Lundbeck & Co AS, Dis Biol, Valby, Denmark
[4] ProteoSys AG, Mainz, Germany
[5] Gothenburg Univ, Dept Med Biophys, Gothenburg, Sweden
[6] Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden
关键词
asialoerythropoietin; erythropoietin; hypoxia; ischemia; neonatal; neuroprotection;
D O I
10.1111/j.1471-4159.2004.02769.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recently, erythropoietin (EPO) and the nonerythropoietic derivative asialoEPO have been linked to tissue protection in the nervous system. In this study, we tested their effects in a model of neonatal hypoxia-ischemia (HI) in 7-day-old rats (unilateral carotid ligation and exposure to 7.7% O-2 for 50 min). EPO (10 U/g body weight = 80 ng/g; n = 24), asialoEPO (80 ng/g; n = 23) or vehicle (phosphate-buffered saline with 0.1% human serum albumin; n = 24) was injected intraperitoneally 4 h before HI. Both drugs were protective, as judged by measuring the infarct volumes, neuropathological score and gross morphological score. The infarct volumes were significantly reduced by both EPO (52%) and asialoEPO (55%) treatment, even though the plasma levels of asialoEPO had dropped below the detection limit (1 pm) at the onset of HI, while those of EPO were in the nanomolar range. Thus, a brief trigger by asialoEPO before the insult appears to be sufficient for protection. Proteomics analysis after asialoEPO treatment alone (no HI) revealed at least one differentially up-regulated protein, synaptosome-associated protein of 25 kDa (SNAP-25). Activation (phosphorylation) of ERK was significantly reduced in asialoEPO-treated animals after HI. EPO and the nonerythropoietic asialoEPO both provided significant and equal neuroprotection when administered 4 h prior to HI in 7-day-old rats. The protection might be related to reduced ERK activation and up-regulation of SNAP-25.
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收藏
页码:900 / 910
页数:11
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