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Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension

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Author(s)
Mi Ra Noh Min Jung Kong Sang Jun Han Jee In Kim Kwon Moo Park
Keimyung Author(s)
Kim, Jee In
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Redox Biology
Issued Date
2020
Volume
34
Keyword
Isocitrate dehydrogenase 2HypertensionMitochondriaReactive oxygen speciesRenin-angiotensin system
Abstract
The development of hypertension is associated with mitochondrial redox balance disruptions. NADP+-dependent isocitrate dehydrogenase 2 (IDH2) plays an important role in the maintenance of mitochondrial redox balance by producing mitochondrial NADPH, which is an essential cofactor in the reduction of glutathione (from GSSG to GSH) to reduced form of glutathione (GSH). We investigated the association of IDH2 between the development of prolonged high-fat diet (HFD)-induced hypertension. Idh2 gene-deleted (Idh2-/-) male mice and wild-type (Idh2+/+) littermates were fed either HFD or low-fat diet (LFD). Some mice were administrated with Mito-TEMPO, a mitochondria-specific antioxidant. HFD feeding increased blood pressure (BP) in both Idh2-/- mice and Idh2+/+ mice. HFD-induced BP increase was greater in Idh2-/- than Idh2+/+ mice. HFD intake decreased IDH2 activity, NADPH levels, and the GSH/(GSH + GSSG) ratio in the renal mitochondria. However, HFD intake increased mitochondrial ROS levels, along with the accompanying oxidative stress and damage. HFD intake increased angiotensin II receptor 1 type 1 mRNA levels in the kidneys and plasma renin and angiotensin II concentrations. These HFD-induced changes were more prominent in Idh2-/- mice than Idh2+/+ mice. Mito-TEMPO mitigated the HFD-induced changes in both Idh2-/- and Idh2+/+ mice, with greater effects in Idh2-/- mice than Idh2+/+ mice. These results indicate that prolonged HFD intake disrupts the IDH2-NADPH-GSH-associated antioxidant system and activates the renin-angiotensin system in the kidney, leading to increased BP, suggesting that IDH2 is a critical enzyme in the development of hypertension and that the IDH2-associated antioxidant system could serve as a potential hypertension treatment target.
Keimyung Author(s)(Kor)
김지인
Publisher
School of Medicine (의과대학)
Citation
Mi Ra Noh et al. (2020). Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension. Redox Biology, 34, 101548. doi: 10.1016/j.redox.2020.101548
Type
Article
ISSN
2213-2317
Source
https://www.sciencedirect.com/science/article/pii/S2213231720304742
DOI
10.1016/j.redox.2020.101548
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43288
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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