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

作者:Chung Hee Kyoung; Ko Eun Mi; Kim Sung Woo; Byun Sung June; Chung Hak Jae; Kwon Moosik; Lee Hwi Cheul; Yang Byoung Chul; Han Deug Woo; Park Jin Ki; Hong Sung Gu; Chang Won Kyong*; Kim Kyung Woon
来源:BMB Reports, 2012, 45(12): 742-747.
DOI:10.5483/BMBRep.2012.45.12.095

摘要

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]

  • 出版日期2012-12-31