Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes.

Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes.
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DOI:
10.5483/bmbrep.2012.45.12.095
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发表时间:
2012-12
期刊:
影响因子:
3.8
通讯作者:
Kim KW
Kim KW
中科院分区:
生物学3区
文献类型:
--
作者:
Chung HK;Ko EM;Kim SW;Byun SJ;Chung HJ;Kwon M;Lee HC;Yang BC;Han DW;Park JK;Hong SG;Chang WK;Kim KW

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粒细胞集落刺激因子(G-CSF)用于心力衰竭治疗,并通过诱导骨髓干细胞动员到心肌梗死后受损的心脏来促进心肌再生;然而,这种治疗有一个缺点,即其生物学效应是短暂的。在我们以前的报告中,我们产生了5个突变体窝藏N-连接的糖基化,以提高其抗凋亡活性。其中,一个突变体(Phe 140 Asn)有更高的细胞活力比野生型hG-CSF在大鼠心肌细胞,即使用凋亡剂(H2 O2)处理后。用这种突变体处理的细胞显著上调抗凋亡蛋白,并经历了caspase 3活性和PARP裂解的降低。此外,在用突变型hG-CSF处理的培养物中,凋亡细胞的总数显著降低。总之,这些结果表明,添加N-连接的糖基化成功地改善了hG-CSF的抗凋亡活性,并且这种突变产物将是经历心力衰竭的患者的可行疗法。[BMB报告2012; 45(12):742-747]
Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent (H2O2). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure. [BMB Reports 2012; 45(12): 742-747]
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