Journal article
IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function
Free radical biology & medicine, Vol.94, pp.36-46
05/01/2016
DOI: 10.1016/j.freeradbiomed.2016.02.017
PMID: 26898144
Abstract
Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and cancer cells. However, the function of IDH2 in vascular endothelial cells is mostly unknown. In this study the effects of IDH2 deficiency on mitochondrial and vascular function were investigated in endothelial cells. IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial-specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown-induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function. (C) 2016 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function
- Creators
- Jung-Bum Park - Chungnam National UniversityHarsha Nagar - Chungnam National UniversitySujeong Choi - Chungnam National UniversitySaet-byel Jung - Chungnam National UniversityHyun-Woo Kim - Chungnam National UniversityShin Kwang Kang - Chungnam National UniversityJun Wan Lee - Chungnam National UniversityJin Hyup Lee - Dept. of Food and Biotechnology Korea Univ Sejong 339‐700 Republic of KoreaJeen-Woo Park - Kyungpook National UniversityKaikobad Irani - Roy J. and Lucille A. Carver College of MedicineByeong Hwa Jeon - Chungnam National UniversityHee-Jung Song - Chungnam National UniversityCuk-Seong Kim - Chungnam National University
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.94, pp.36-46
- DOI
- 10.1016/j.freeradbiomed.2016.02.017
- PMID
- 26898144
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- Korean Health Technology R&D Project through the Korean Health Industry Development Institute KHI13C1990010013 / Ministry of Health & Welfare, Republic of Korea P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NRF-2014R1A6A1029617; NRF-2015R1D1A1A01061516 / Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education
- Language
- English
- Date published
- 05/01/2016
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984312965802771
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