PMID- 26505347
OWN - NLM
STAT- MEDLINE
DCOM- 20160413
LR  - 20220408
IS  - 1676-5680 (Electronic)
IS  - 1676-5680 (Linking)
VI  - 14
IP  - 4
DP  - 2015 Oct 5
TI  - AMP-activated protein kinase regulates autophagic protection against 
      cisplatin-induced tissue injury in the kidney.
PG  - 12006-15
LID - 10.4238/2015.October.5.13 [doi]
AB  - Although the nephrotoxicity of cisplatin has been well documented as a major side 
      effect of chemotherapy, the exact mechanism by which prosurvival and apoptotic 
      pathways interplay to determine renal pathology remains elusive. Recent studies 
      suggested that autophagy might serve as an adaptive mechanism to promote cell 
      survival during acute kidney injury (AKI). We have used AKI as a disease model to 
      investigate the mechanism regulating the cytoprotective role of autophagy in 
      cisplatin-induced tissue damage. Pharmacological inhibitors such as chloroquine 
      were used to manipulate autophagy during AKI, and DNA damage was evaluated by 
      using the cellular marker gammaH2AX. Cisplatin induced extensive DNA damage during 
      AKI. Autophagy activation served as a survival strategy to suppress 
      cisplatin-induced DNA damage in the pathology of AKI both in vitro and in vivo. 
      Interestingly, in the kidney, cisplatin treatment can activate AMP-activated 
      protein kinase (AMPK), a signaling molecule that is also critical for 
      p53-mediated inactivation of mammalian target of rapamycin (mTOR) pathways. As a 
      result, inhibition or knockdown of AMPK can lead to repressed autophagy in 
      cisplatin-induced AKI, resulting in more DNA damage. Activation of AMPK regulates 
      autophagy during cisplatin-induced AKI. Given the fact that p53 can regulate 
      autophagy by inactivating mTOR via AMPK, our results suggest that the p53 pathway 
      may also play a critical role in the pathogenesis of cisplatin-induced renal 
      damage. This study may further our understanding of the physiological roles of 
      autophagy in the pathogenesis of renal injuries, and thus may have pathological 
      implications in the clinical setting.
FAU - Wei, L
AU  - Wei L
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Chen, W
AU  - Chen W
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Zou, Y
AU  - Zou Y
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Huang, H
AU  - Huang H
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Pan, B
AU  - Pan B
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Jin, S
AU  - Jin S
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China.
FAU - Huang, R
AU  - Huang R
AD  - Institute of Clinical Medical Research, Hunan Provincial People's Hospital, 
      Changsha, Hunan, China.
FAU - Nie, S
AU  - Nie S
AD  - Institute of Clinical Medical Research, Hunan Provincial People's Hospital, 
      Changsha, Hunan, China.
FAU - Kong, G
AU  - Kong G
AD  - Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, 
      Hunan, China gyk_hn@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151005
PL  - Brazil
TA  - Genet Mol Res
JT  - Genetics and molecular research : GMR
JID - 101169387
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Acute Kidney Injury/etiology/*metabolism
MH  - Animals
MH  - *Autophagy
MH  - Cells, Cultured
MH  - Cisplatin/*toxicity
MH  - DNA Damage
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 2015/10/28 06:00
MHDA- 2016/04/14 06:00
CRDT- 2015/10/28 06:00
PHST- 2015/10/28 06:00 [entrez]
PHST- 2015/10/28 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
AID - gmr6157 [pii]
AID - 10.4238/2015.October.5.13 [doi]
PST - epublish
SO  - Genet Mol Res. 2015 Oct 5;14(4):12006-15. doi: 10.4238/2015.October.5.13.