Functional alteration of canine isocitrate dehydrogenase 2 (IDH2) via an R174K mutation
| العنوان: | Functional alteration of canine isocitrate dehydrogenase 2 (IDH2) via an R174K mutation |
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| المؤلفون: | Masaki Michishita, Shota Kawakami, Ryo Obara, Kazuhiko Ochiai, Hinako Hirama, Daigo Azakami, Yuiko Kato, Masami Watanabe, Toshinori Omi |
| المصدر: | The Journal of Veterinary Medical Science |
| بيانات النشر: | Japanese Society of Veterinary Science, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Somatic cell, Clone (cell biology), canine, Transfection, medicine.disease_cause, Biochemistry, IDH2, Madin Darby Canine Kidney Cells, HeLa, 03 medical and health sciences, Dogs, 0302 clinical medicine, glioma, Complementary DNA, medicine, Animals, Humans, Mutation, Full Paper, General Veterinary, biology, Brain Neoplasms, Chemistry, Wild type, NAD, biology.organism_classification, Molecular biology, Isocitrate Dehydrogenase, 030104 developmental biology, 030220 oncology & carcinogenesis, Carcinogenesis, NADP, HeLa Cells |
| الوصف: | Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K). The cIDH2 WT and R174K proteins were overexpressed in HeLa cells, and their presence was confirmed using an anti-human IDH2-WT mAb (clone: KrMab-3) and an anti-IDH2-R172K mAb (clone: KMab-1). The IDH2 activity between cIDH2 WT and cIDH2 R174K transfectants was compared by measuring the production of NADH and NADPH. NADPH production was lower for cIDH2 R174K than that for cIDH2 WT transfectants. Finally, we detected increased expression of hypoxia inducible factor-1 alpha (HIF-1α) in cIDH2 R174K transfectants. This indicates that mutations at R174 can potentially induce carcinogenesis in canine somatic cells. |
| تدمد: | 1347-7439 0916-7250 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eaf52b7c5fb3b79380ab91bce6e6c061 https://doi.org/10.1292/jvms.17-0362 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eaf52b7c5fb3b79380ab91bce6e6c061 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13477439 09167250 |
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