PMID- 19436334
OWN - NLM
STAT- MEDLINE
DCOM- 20100122
LR  - 20211020
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 76
IP  - 3
DP  - 2009 Aug
TI  - Transcription factor Nrf2 is protective during ischemic and nephrotoxic acute 
      kidney injury in mice.
PG  - 277-85
LID - 10.1038/ki.2009.157 [doi]
AB  - Oxidative stress is involved in acute kidney injury due to ischemia-reperfusion 
      and chemotherapy-induced nephrotoxicity. To investigate their basic mechanisms we 
      studied the role of nuclear factor-erythroid 2-p45-related factor 2 (Nrf2), a 
      redox-sensitive transcription factor that regulates expression of several 
      antioxidant and cytoprotective genes. We compared the responses of Nrf2-knockout 
      mice and their wild-type littermates in established mouse models of 
      ischemia-reperfusion injury and cisplatin-induced nephrotoxicity. Several 
      Nrf2-regulated genes encoding antioxidant enzymes/proteins were significantly 
      upregulated in the kidneys of wild type but not Nrf2-knockout mice following 
      renal ischemia. Renal function, histology, vascular permeability, and survival 
      were each significantly worse in the Nrf2 knockout mice. Further, proinflammatory 
      cytokine and chemokine expression tended to increase after ischemia in the 
      knockout compared to the wild-type mice. Treatment of the knockout mice with the 
      antioxidants N-acetyl-cysteine or glutathione improved renal function. The 
      knockout mice were more susceptible to cisplatin-induced nephrotoxicity, and this 
      was blunted by N-acetyl-cysteine pretreatment. Our study demonstrates that 
      Nrf2-deficiency enhances susceptibility to both ischemic and nephrotoxic acute 
      kidney injury, and identifies this transcription factor as a potential 
      therapeutic target in these injuries.
FAU - Liu, Manchang
AU  - Liu M
AD  - Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, 
      Maryland 21205, USA. mliu13@jhmi.edu
FAU - Grigoryev, Dmitry N
AU  - Grigoryev DN
FAU - Crow, Michael T
AU  - Crow MT
FAU - Haas, Mark
AU  - Haas M
FAU - Yamamoto, Masayuki
AU  - Yamamoto M
FAU - Reddy, Sekhar P
AU  - Reddy SP
FAU - Rabb, Hamid
AU  - Rabb H
LA  - eng
GR  - R01 DK084445/DK/NIDDK NIH HHS/United States
GR  - 2R01 DK54770/DK/NIDDK NIH HHS/United States
GR  - P0 HL073944/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090513
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - GAN16C9B8O (Glutathione)
RN  - Q20Q21Q62J (Cisplatin)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Acute Kidney Injury/chemically induced/*metabolism/pathology
MH  - Animals
MH  - Antineoplastic Agents/toxicity
MH  - Capillary Permeability
MH  - Cisplatin/toxicity
MH  - Glutathione/pharmacology
MH  - Inflammation Mediators/metabolism
MH  - Kidney/pathology
MH  - Kidney Function Tests
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Reperfusion Injury/*metabolism
MH  - Up-Regulation
EDAT- 2009/05/14 09:00
MHDA- 2010/01/23 06:00
CRDT- 2009/05/14 09:00
PHST- 2009/05/14 09:00 [entrez]
PHST- 2009/05/14 09:00 [pubmed]
PHST- 2010/01/23 06:00 [medline]
AID - S0085-2538(15)53959-8 [pii]
AID - 10.1038/ki.2009.157 [doi]
PST - ppublish
SO  - Kidney Int. 2009 Aug;76(3):277-85. doi: 10.1038/ki.2009.157. Epub 2009 May 13.