PMID- 25898836
OWN - NLM
STAT- MEDLINE
DCOM- 20160419
LR  - 20220408
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 240
IP  - 12
DP  - 2015 Dec
TI  - Autophagy activation attenuates renal ischemia-reperfusion injury in rats.
PG  - 1590-8
LID - 10.1177/1535370215581306 [doi]
AB  - Ischemia-reperfusion (I/R) injury is a leading cause of acute kidney injury 
      (AKI), which is a common clinical complication but lacks effective therapies. 
      This study investigated the role of autophagy in renal I/R injury and explored 
      potential mechanisms in an established rat renal I/R injury model. Forty male 
      Wistar rats were randomly divided into four groups: Sham, I/R, I/R pretreated 
      with 3-methyladenine (3-MA, autophagy inhibitor), or I/R pretreated with 
      rapamycin (autophagy activator). All rats were subjected to clamping of the left 
      renal pedicle for 45 min after right nephrectomy, followed by 24 h of 
      reperfusion. The Sham group underwent the surgical procedure without ischemia. 
      3-MA and rapamycin were injected 15 min before ischemia. Renal function was 
      indicated by blood urea nitrogen and serum creatinine. Tissue samples from the 
      kidneys were scored histopathologically. Autophagy was indicated by light chain 3 
      (LC3), Beclin-1, and p62 levels and the number of autophagic vacuoles. Apoptosis 
      was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) method and expression of caspase-3. Autophagy was activated 
      after renal I/R injury. Inhibition of autophagy by 3-MA before I/R aggravated 
      renal injury, with worsened renal function, higher renal tissue injury scores, 
      and more tubular apoptosis. In contrast, rapamycin pretreatment ameliorated renal 
      injury, with improved renal function, lower renal tissue injury scores, and 
      inhibited apoptosis based on fewer TUNEL-positive cells and lower caspase-3 
      expression. Our results demonstrate that autophagy could be activated during I/R 
      injury and play a protective role in renal I/R injury. The mechanisms were 
      involved in the regulation of several autophagy and apoptosis-related genes. 
      Furthermore, autophagy activator may be a promising therapy for I/R injury and 
      AKI in the future.
CI  - (c) 2015 by the Society for Experimental Biology and Medicine.
FAU - Zhang, Ya-Li
AU  - Zhang YL
AD  - Department of Laboratory Medicine, Peking University Third Hospital, Beijing 
      100191, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Department of Laboratory Medicine, Peking University Third Hospital, Beijing 
      100191, China bjmuzhangjie@sina.com.
FAU - Cui, Li-Yan
AU  - Cui LY
AD  - Department of Laboratory Medicine, Peking University Third Hospital, Beijing 
      100191, China.
FAU - Yang, Shuo
AU  - Yang S
AD  - Department of Laboratory Medicine, Peking University Third Hospital, Beijing 
      100191, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150421
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 5142-23-4 (3-methyladenine)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 3.4.22.- (Caspase 3)
RN  - JAC85A2161 (Adenine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Acute Kidney Injury/etiology/*physiopathology
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Autophagy/drug effects/*physiology
MH  - Blood Urea Nitrogen
MH  - Caspase 3/metabolism
MH  - Creatinine/blood
MH  - Disease Models, Animal
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/complications/*physiopathology
MH  - Sirolimus/pharmacology
PMC - PMC4935330
OTO - NOTNLM
OT  - Autophagy
OT  - acute kidney injury
OT  - apoptosis
OT  - ischemia reperfusion
EDAT- 2015/04/23 06:00
MHDA- 2016/04/20 06:00
PMCR- 2016/06/01
CRDT- 2015/04/23 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2015/02/24 00:00 [accepted]
PHST- 2015/04/23 06:00 [entrez]
PHST- 2015/04/23 06:00 [pubmed]
PHST- 2016/04/20 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 1535370215581306 [pii]
AID - 10.1177_1535370215581306 [pii]
AID - 10.1177/1535370215581306 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2015 Dec;240(12):1590-8. doi: 10.1177/1535370215581306. 
      Epub 2015 Apr 21.