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IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages
Mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilatera...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893493/ https://www.ncbi.nlm.nih.gov/pubmed/33602884 http://dx.doi.org/10.4196/kjpp.2021.25.2.139 |
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author | Kim, Jee In Noh, Mi Ra Yoon, Ga-Eun Jang, Hee-Seong Kong, Min Jung Park, Kwon Moo |
author_facet | Kim, Jee In Noh, Mi Ra Yoon, Ga-Eun Jang, Hee-Seong Kong, Min Jung Park, Kwon Moo |
author_sort | Kim, Jee In |
collection | PubMed |
description | Mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2(–/–)). Eight- to 10-week-old female IDH2(–/–) mice and wild type (IDH2(+/+)) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2(–/–) mice, while UUO decreased IDH2 in IDH2(+/+) mice. UUO increased the expressions of markers of oxidative stress in both IDH2(+/+) and IDH2(–/–) mice, and these changes were greater in IDH2(–/–) mice compared to IDH2(+/+) mice. Bone marrow-derived macrophages of IDH2(–/–) mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2(+/+) mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2(–/–) mice compared to IDH2(+/+) mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration. |
format | Online Article Text |
id | pubmed-7893493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78934932021-03-01 IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages Kim, Jee In Noh, Mi Ra Yoon, Ga-Eun Jang, Hee-Seong Kong, Min Jung Park, Kwon Moo Korean J Physiol Pharmacol Original Article Mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2(–/–)). Eight- to 10-week-old female IDH2(–/–) mice and wild type (IDH2(+/+)) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2(–/–) mice, while UUO decreased IDH2 in IDH2(+/+) mice. UUO increased the expressions of markers of oxidative stress in both IDH2(+/+) and IDH2(–/–) mice, and these changes were greater in IDH2(–/–) mice compared to IDH2(+/+) mice. Bone marrow-derived macrophages of IDH2(–/–) mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2(+/+) mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2(–/–) mice compared to IDH2(+/+) mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration. The Korean Physiological Society and The Korean Society of Pharmacology 2021-03-01 2021-03-01 /pmc/articles/PMC7893493/ /pubmed/33602884 http://dx.doi.org/10.4196/kjpp.2021.25.2.139 Text en Copyright © Korean J Physiol Pharmacol This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Jee In Noh, Mi Ra Yoon, Ga-Eun Jang, Hee-Seong Kong, Min Jung Park, Kwon Moo IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title | IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title_full | IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title_fullStr | IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title_full_unstemmed | IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title_short | IDH2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
title_sort | idh2 gene deficiency accelerates unilateral ureteral obstruction-induced kidney inflammation through oxidative stress and activation of macrophages |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893493/ https://www.ncbi.nlm.nih.gov/pubmed/33602884 http://dx.doi.org/10.4196/kjpp.2021.25.2.139 |
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