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http://dx.doi.org/10.5483/BMBRep.2012.45.12.095

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

Chung, Hee Kyoung (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Ko, Eun Mi (Post-harvest & Food Engineering Division, Department of Agricultural Engineering, National Academy of Agricultural Science)
Kim, Sung Woo (Animal Genetic Resources Station, National Institute of Animal Science, Rural Development Administration)
Byun, Sung-June (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Chung, Hak-Jae (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Kwon, Moosik (Department of Genetic Engineering, Sungkyunkwan University)
Lee, Hwi-Cheul (Planning & Coordination Division, National Institute of Animal Science, Rural Development Administration)
Yang, Byoung-Chul (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Han, Deug-Woo (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Park, Jin-Ki (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Hong, Sung-Gu (National Institute of Animal Science, Rural Development Administration)
Chang, Won-Kyong (National Institute of Animal Science, Rural Development Administration)
Kim, Kyung-Woon (Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration)
Publication Information
BMB Reports / v.45, no.12, 2012 , pp. 742-747 More about this Journal
Abstract
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 ($H_2O_2$). 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.
Keywords
Antiapoptotic activity; Heart failure; hG-CSF (Phe140Asn);
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