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 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.
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, The People's Republic of China; Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America; Key Laboratory of Ministry of Health and Key Laboratory of Ministry of Education, Wuhan, HuBei, The People's Republic of China.
Bo
B
Zhang
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Daniel
D
Cowden
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Neurosurgery, Shandong University, Shandong provincial hospital, Jinan, The People's Republic of China; Department of Neurosurgery, Chengdu First People's Hospital, Chengdu, The People's Republic of China.
Fan
F
Zhang
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Jue
J
Yuan
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Sandra
S
Siedlak
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Mai
M
Abouelsaad
Department of Urology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China; Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Liang
L
Zeng
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
Xuefeng
X
Zhou
Kidney Disease Research Center, Case Western Reserve University, Cleveland, Ohio, United States of America; Departments of Medicine and Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America.
John
J
O'Toole
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Alvin S
AS
Das
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Diane
D
Kofskey
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Miriam
M
Warren
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
Zehua
Z
Bian
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
Yuqi
Y
Cui
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
Tao
T
Tan
Human Tissue Procurement Facility (HTPF) and the Comprehensive Cancer Center Tissue Resources Core, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States of America.
Adam
A
Kresak
Human Tissue Procurement Facility (HTPF) and the Comprehensive Cancer Center Tissue Resources Core, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States of America.
Robert E
RE
Wyza
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Neurology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Neuroscience, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Robert B
RB
Petersen
Department of Urology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
Gong-Xian
GX
Wang
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Neurology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; National Center for Regenerative Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Qingzhong
Q
Kong
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Xinglong
X
Wang
Kidney Disease Research Center, Case Western Reserve University, Cleveland, Ohio, United States of America; Departments of Medicine and Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America.
John
J
Sedor
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Xiongwei
X
Zhu
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
Hua
H
Zhu
Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Urology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China; National Prion Disease Pathology Surveillance Center, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Neurology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; National Center for Regenerative Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, The People's Republic of China.
Wen-Quan
WQ
Zou
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011328:Prions / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D011328:Prions; C002744:3-nitrotyrosine; D014443:Tyrosine; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases