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KMID : 0624620120450120742
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BMB Reports
2012 Volume.45 No. 12 p.742 ~ p.747
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Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes
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Chung Hee-Kyoung
Ko Eun-Mi
Kim Sung-Woo
Byun Sung-June
Chung Hak-Jae
Kwon Moo-Sik
Lee Hwi-Cheul
Yang Byoung-Chul
Han Deug-Woo
Park Jin-Ki
Hong Sung-Gu
Chang Won-Kyong
Kim Kyung-Woon
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Abstract
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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.
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KEYWORD
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Antiapoptotic activity, Heart failure, hG-CSF (Phe140Asn)
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