Prion Protein Protects against Renal Ischemia/Reperfusion Injury.
The cellular prion protein (PrPC), a protein most noted for its link to prion diseases, has been found to play a protective role in ischemic brain injury. To investigate the role of PrPC in the kidney, an organ highly prone to ischemia/reperfusion (IR) injury, we examined wild-type (WT) and PrPC kno...
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doaj-bcb57bbb317d4e0ba912d71adf48e6b82020-11-25T01:31:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013692310.1371/journal.pone.0136923Prion Protein Protects against Renal Ischemia/Reperfusion Injury.Bo ZhangDaniel CowdenFan ZhangJue YuanSandra SiedlakMai AbouelsaadLiang ZengXuefeng ZhouJohn O'TooleAlvin S DasDiane KofskeyMiriam WarrenZehua BianYuqi CuiTao TanAdam KresakRobert E WyzaRobert B PetersenGong-Xian WangQingzhong KongXinglong WangJohn SedorXiongwei ZhuHua ZhuWen-Quan ZouThe cellular prion protein (PrPC), a protein most noted for its link to prion diseases, has been found to play a protective role in ischemic brain injury. To investigate the role of PrPC in the kidney, an organ highly prone to ischemia/reperfusion (IR) injury, we examined wild-type (WT) and PrPC knockout (KO) mice that were subjected to 30-min of renal ischemia followed by 1, 2, or 3 days of reperfusion. Renal dysfunction and structural damage was more severe in KO than in WT mice. While PrP was undetectable in KO kidneys, Western blotting revealed an increase in PrP in IR-injured WT kidneys compared to sham-treated kidneys. Compared to WT, KO kidneys exhibited increases in oxidative stress markers heme oxygenase-1, nitrotyrosine, and Nε-(carboxymethyl)lysine, and decreases in mitochondrial complexes I and III. Notably, phosphorylated extracellular signal-regulated kinase (pERK) staining was predominantly observed in tubular cells from KO mice following 2 days of reperfusion, a time at which significant differences in renal dysfunction, histological changes, oxidative stress, and mitochondrial complexes between WT and KO mice were observed. Our study provides the first evidence that PrPC may play a protective role in renal IR injury, likely through its effects on mitochondria and ERK signaling pathways.http://europepmc.org/articles/PMC4556704?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Zhang Daniel Cowden Fan Zhang Jue Yuan Sandra Siedlak Mai Abouelsaad Liang Zeng Xuefeng Zhou John O'Toole Alvin S Das Diane Kofskey Miriam Warren Zehua Bian Yuqi Cui Tao Tan Adam Kresak Robert E Wyza Robert B Petersen Gong-Xian Wang Qingzhong Kong Xinglong Wang John Sedor Xiongwei Zhu Hua Zhu Wen-Quan Zou |
spellingShingle |
Bo Zhang Daniel Cowden Fan Zhang Jue Yuan Sandra Siedlak Mai Abouelsaad Liang Zeng Xuefeng Zhou John O'Toole Alvin S Das Diane Kofskey Miriam Warren Zehua Bian Yuqi Cui Tao Tan Adam Kresak Robert E Wyza Robert B Petersen Gong-Xian Wang Qingzhong Kong Xinglong Wang John Sedor Xiongwei Zhu Hua Zhu Wen-Quan Zou Prion Protein Protects against Renal Ischemia/Reperfusion Injury. PLoS ONE |
author_facet |
Bo Zhang Daniel Cowden Fan Zhang Jue Yuan Sandra Siedlak Mai Abouelsaad Liang Zeng Xuefeng Zhou John O'Toole Alvin S Das Diane Kofskey Miriam Warren Zehua Bian Yuqi Cui Tao Tan Adam Kresak Robert E Wyza Robert B Petersen Gong-Xian Wang Qingzhong Kong Xinglong Wang John Sedor Xiongwei Zhu Hua Zhu Wen-Quan Zou |
author_sort |
Bo Zhang |
title |
Prion Protein Protects against Renal Ischemia/Reperfusion Injury. |
title_short |
Prion Protein Protects against Renal Ischemia/Reperfusion Injury. |
title_full |
Prion Protein Protects against Renal Ischemia/Reperfusion Injury. |
title_fullStr |
Prion Protein Protects against Renal Ischemia/Reperfusion Injury. |
title_full_unstemmed |
Prion Protein Protects against Renal Ischemia/Reperfusion Injury. |
title_sort |
prion protein protects against renal ischemia/reperfusion injury. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
The cellular prion protein (PrPC), a protein most noted for its link to prion diseases, has been found to play a protective role in ischemic brain injury. To investigate the role of PrPC in the kidney, an organ highly prone to ischemia/reperfusion (IR) injury, we examined wild-type (WT) and PrPC knockout (KO) mice that were subjected to 30-min of renal ischemia followed by 1, 2, or 3 days of reperfusion. Renal dysfunction and structural damage was more severe in KO than in WT mice. While PrP was undetectable in KO kidneys, Western blotting revealed an increase in PrP in IR-injured WT kidneys compared to sham-treated kidneys. Compared to WT, KO kidneys exhibited increases in oxidative stress markers heme oxygenase-1, nitrotyrosine, and Nε-(carboxymethyl)lysine, and decreases in mitochondrial complexes I and III. Notably, phosphorylated extracellular signal-regulated kinase (pERK) staining was predominantly observed in tubular cells from KO mice following 2 days of reperfusion, a time at which significant differences in renal dysfunction, histological changes, oxidative stress, and mitochondrial complexes between WT and KO mice were observed. Our study provides the first evidence that PrPC may play a protective role in renal IR injury, likely through its effects on mitochondria and ERK signaling pathways. |
url |
http://europepmc.org/articles/PMC4556704?pdf=render |
work_keys_str_mv |
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