Cargando…

CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress

BACKGROUND: Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic ne...

Descripción completa

Detalles Bibliográficos
Autores principales: Hua, Wei, Huang, Hui-zhe, Tan, Lan-ting, Wan, Jiang-min, Gui, Hai-bo, Zhao, Liang, Ruan, Xiong-zhong, Chen, Xue-mei, Du, Xiao-gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441449/
https://www.ncbi.nlm.nih.gov/pubmed/26000608
http://dx.doi.org/10.1371/journal.pone.0127507
_version_ 1782372793265946624
author Hua, Wei
Huang, Hui-zhe
Tan, Lan-ting
Wan, Jiang-min
Gui, Hai-bo
Zhao, Liang
Ruan, Xiong-zhong
Chen, Xue-mei
Du, Xiao-gang
author_facet Hua, Wei
Huang, Hui-zhe
Tan, Lan-ting
Wan, Jiang-min
Gui, Hai-bo
Zhao, Liang
Ruan, Xiong-zhong
Chen, Xue-mei
Du, Xiao-gang
author_sort Hua, Wei
collection PubMed
description BACKGROUND: Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN), respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated. METHODS: The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20) by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5) and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software. RESULTS: CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO), the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol) inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid. CONCLUSIONS: CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.
format Online
Article
Text
id pubmed-4441449
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-44414492015-05-28 CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress Hua, Wei Huang, Hui-zhe Tan, Lan-ting Wan, Jiang-min Gui, Hai-bo Zhao, Liang Ruan, Xiong-zhong Chen, Xue-mei Du, Xiao-gang PLoS One Research Article BACKGROUND: Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN), respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated. METHODS: The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20) by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5) and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software. RESULTS: CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO), the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol) inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid. CONCLUSIONS: CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN. Public Library of Science 2015-05-22 /pmc/articles/PMC4441449/ /pubmed/26000608 http://dx.doi.org/10.1371/journal.pone.0127507 Text en © 2015 Hua et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hua, Wei
Huang, Hui-zhe
Tan, Lan-ting
Wan, Jiang-min
Gui, Hai-bo
Zhao, Liang
Ruan, Xiong-zhong
Chen, Xue-mei
Du, Xiao-gang
CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title_full CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title_fullStr CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title_full_unstemmed CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title_short CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
title_sort cd36 mediated fatty acid-induced podocyte apoptosis via oxidative stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441449/
https://www.ncbi.nlm.nih.gov/pubmed/26000608
http://dx.doi.org/10.1371/journal.pone.0127507
work_keys_str_mv AT huawei cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT huanghuizhe cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT tanlanting cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT wanjiangmin cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT guihaibo cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT zhaoliang cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT ruanxiongzhong cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT chenxuemei cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress
AT duxiaogang cd36mediatedfattyacidinducedpodocyteapoptosisviaoxidativestress