PMID- 37507979
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230731
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 7
DP  - 2023 Jul 18
TI  - Impaired NRF2 Inhibits Recovery from Ischemic Reperfusion Injury in the Aging 
      Kidney.
LID - 10.3390/antiox12071440 [doi]
LID - 1440
AB  - Deteriorating kidney function is frequently observed in the elderly population, 
      as well as vulnerability to acute kidney failure, such as ischemic/reperfusion 
      injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney 
      dysfunction in the elderly. The potential mediators in the progression of kidney 
      dysfunction in the aging kidney have not yet been clearly revealed. In this 
      study, we investigated the role of nuclear factor erythroid 2-related factor 2 
      (NRF2), which is an essential regulator of cellular redox homeostasis, in 
      restoring kidney function after IRI in the aging kidney. NRF2 expression 
      decreased significantly in the kidneys of old mice, as well as histologic and 
      functional renal recovery after IRI; 45-min renal pedicle clamping was retarded 
      in old compared with young mice. Persistent renal injury during the recovery 
      phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type 
      mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase 
      along with decreased expression of mitochondrial OXPHOS-related proteins and a 
      reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) 
      injury was aggravated in senescent human proximal tubuloepithelial cells after 
      NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative 
      stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 
      activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be 
      a therapeutic target for the aging kidney.
FAU - Jo, Min Jee
AU  - Jo MJ
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
AD  - Convergence Research Center for Development New Drug, Korea University College of 
      Medicine, Seoul 08308, Republic of Korea.
FAU - Kim, Ji Eun
AU  - Kim JE
AUID- ORCID: 0000-0003-3094-2229
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
FAU - Bae, So Yon
AU  - Bae SY
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
FAU - Cho, Eunjung
AU  - Cho E
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
FAU - Ahn, Shin Young
AU  - Ahn SY
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
FAU - Kwon, Young Joo
AU  - Kwon YJ
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
FAU - Ko, Gang-Jee
AU  - Ko GJ
AUID- ORCID: 0000-0001-7927-8651
AD  - Department of Internal Medicine, Korea University College of Medicine, Korea 
      University Guro Hospital, Seoul 08308, Republic of Korea.
LA  - eng
GR  - 2021R1A6A3A01087658/National Research Foundation of Korea/
GR  - 2019R1F1A1062663/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20230718
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10376352
OTO - NOTNLM
OT  - NRF2
OT  - aging
OT  - ischemic reperfusion injury
OT  - recovery from acute kidney injury
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:47
MHDA- 2023/07/29 11:48
PMCR- 2023/07/18
CRDT- 2023/07/29 01:04
PHST- 2023/06/19 00:00 [received]
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2023/07/29 11:48 [medline]
PHST- 2023/07/29 11:47 [pubmed]
PHST- 2023/07/29 01:04 [entrez]
PHST- 2023/07/18 00:00 [pmc-release]
AID - antiox12071440 [pii]
AID - antioxidants-12-01440 [pii]
AID - 10.3390/antiox12071440 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Jul 18;12(7):1440. doi: 10.3390/antiox12071440.