論文

査読有り 国際誌
2018年3月

R132 mutations in canine isocitrate dehydrogenase 1 (IDH1) lead to functional changes.

Veterinary research communications
  • Shota Kawakami
  • ,
  • Kazuhiko Ochiai
  • ,
  • Daigo Azakami
  • ,
  • Yuiko Kato
  • ,
  • Masaki Michishita
  • ,
  • Masami Morimatsu
  • ,
  • Toshina Ishiguro-Oonuma
  • ,
  • Eri Onozawa
  • ,
  • Masami Watanabe
  • ,
  • Toshinori Omi

42
1
開始ページ
49
終了ページ
56
記述言語
英語
掲載種別
DOI
10.1007/s11259-017-9707-8

Glioma is the second most common intracranial neoplasia in dogs, but the pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 1 (IDH1) is frequently mutated in gliomas. Although almost all human IDH1 mutations have been identified as involving the Arg132 codon, few studies have reported structural, functional, and mutational information for canine IDH1. Therefore, in this study, we cloned the canine IDH1 homologue and used PCR mutagenesis to substitute the wildtype (WT) Arg132 with His (R132H) or Ser (R132S). WT and mutated IDH1 were overexpressed in HeLa cells, and their presence was confirmed by immunoblotting and immunocytochemistry using mutation-specific antibodies. The IDH1 activity between WT, R132H, and R132S transfectants was compared by measuring the production of NADH and NADPH. NADPH production in R132H and R132S transfectants was lower than that in WT, but NADH levels were not significantly different. Finally, we detected increased expression of hypoxia inducible factor 1 alpha (HIF-1α) in the R132H and R132S transfectants. These results indicated that the canine IDH1 Arg132 mutation has the potential to induce carcinogenesis in canine somatic cells.

リンク情報
DOI
https://doi.org/10.1007/s11259-017-9707-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29285579

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