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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...

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Autores principales: Kim, Jee In, Noh, Mi Ra, Yoon, Ga-Eun, Jang, Hee-Seong, Kong, Min Jung, Park, Kwon Moo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Physiological Society and The Korean Society of Pharmacology 2021
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.
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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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