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

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...

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Autores principales: Noh, Mi Ra, Kong, Min Jung, Han, Sang Jun, Kim, Jee In, Park, Kwon Moo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210593/
https://www.ncbi.nlm.nih.gov/pubmed/32388270
http://dx.doi.org/10.1016/j.redox.2020.101548
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author Noh, Mi Ra
Kong, Min Jung
Han, Sang Jun
Kim, Jee In
Park, Kwon Moo
author_facet Noh, Mi Ra
Kong, Min Jung
Han, Sang Jun
Kim, Jee In
Park, Kwon Moo
author_sort Noh, Mi Ra
collection PubMed
description 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.
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spelling pubmed-72105932020-05-13 Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension Noh, Mi Ra Kong, Min Jung Han, Sang Jun Kim, Jee In Park, Kwon Moo Redox Biol Research Paper 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. Elsevier 2020-04-25 /pmc/articles/PMC7210593/ /pubmed/32388270 http://dx.doi.org/10.1016/j.redox.2020.101548 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Noh, Mi Ra
Kong, Min Jung
Han, Sang Jun
Kim, Jee In
Park, Kwon Moo
Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title_full Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title_fullStr Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title_full_unstemmed Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title_short Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
title_sort isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210593/
https://www.ncbi.nlm.nih.gov/pubmed/32388270
http://dx.doi.org/10.1016/j.redox.2020.101548
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