title: Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes.
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 (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.
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon 441-706, Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Chung
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Ko
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Kim
authors.forename: Sung-June
authors.initials: SJ
authors.lastname: Byun
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Chung
authors.forename: Moosik
authors.initials: M
authors.lastname: Kwon
authors.forename: Hwi-Cheul
authors.initials: HC
authors.lastname: Lee
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Yang
authors.forename: Deug-Woo
authors.initials: DW
authors.lastname: Han
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Park
authors.forename: Sung-Gu
authors.initials: SG
authors.lastname: Hong
authors.forename: Won-Kyong
authors.initials: WK
authors.lastname: Chang
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3