PMID- 31560869
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20211204
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 863
DP  - 2019 Nov 15
TI  - Pioglitazone protects tubular cells against hypoxia/reoxygenation injury through 
      enhancing autophagy via AMPK-mTOR signaling pathway.
PG  - 172695
LID - S0014-2999(19)30647-8 [pii]
LID - 10.1016/j.ejphar.2019.172695 [doi]
AB  - Pioglitazone (Pio), a peroxisome proliferators-activated receptor-gamma (PPAR-gamma) 
      agonist, may protect against renal ischemia/reperfusion injury (IRI). Recent 
      studies have shown that autophagy plays a protective role in IRI. We aimed to 
      evaluate whether autophagy was involved in pioglitazone-induced protection during 
      tubular cell hypoxia/reoxygenation (H/R). Normal rat kidney proximal tubular 
      cells NRK-52E were subjected to H/R injury, and they were divided into 6 groups: 
      control, control + Pio, H/R, H/R + Pio, H/R + MA, H/R + MA + Pio. 
      Autophagy-related proteins were primarily assessed by Western blot and TUNEL was 
      performed to assess cell apoptosis. Our results showed pioglitazone pretreatment 
      had a cytoprotective effect against H/R injury. The H/R + Pio group had an 
      increased ratio of LC3-II to LC3-I and increased Beclin-1, decreased p62. 
      Pioglitazone also reduced apoptosis and enhanced cell survival while inducing 
      autophagy. Correspondingly, autophagy inhibition with 3-MA alleviated this 
      protective effect. Furthermore, pioglitazone-induced enhancement of autophagy 
      could be related to increased AMP-activated protein kinase (AMPK) phosphorylation 
      and decreased Mammalian target of rapamycin (mTOR) phosphorylation. Thus, 
      pioglitazone pretreatment protects against H/R injury by enhancting autophagy 
      through the AMPK-mTOR signaling pathway.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Xi, Xiaoqing
AU  - Xi X
AD  - Department of Urology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, PR China.
FAU - Zou, Cong
AU  - Zou C
AD  - Department of Endocrinology, The Fourth Affiliated Hospital of Nanchang 
      University, Nanchang, PR China.
FAU - Ye, Zhenfeng
AU  - Ye Z
AD  - Department of Urology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, PR China.
FAU - Huang, Yawei
AU  - Huang Y
AD  - Department of Urology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, PR China.
FAU - Chen, Tongchang
AU  - Chen T
AD  - Department of Urology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, PR China.
FAU - Hu, Honglin
AU  - Hu H
AD  - Department of Urology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, PR China. Electronic address: honglinhu@126.com.
LA  - eng
PT  - Journal Article
DEP - 20190924
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - S88TT14065 (Oxygen)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Hypoxia/drug effects
MH  - Cell Line
MH  - Cytoprotection/drug effects
MH  - Kidney Tubules/*cytology/drug effects/metabolism
MH  - Oxygen/*metabolism
MH  - Pioglitazone/*pharmacology
MH  - Rats
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - AMP
OT  - Autophagy
OT  - Hypoxia/reoxygenation
OT  - Pioglitazone
OT  - Tubular cells
EDAT- 2019/09/29 06:00
MHDA- 2020/03/24 06:00
CRDT- 2019/09/28 06:00
PHST- 2019/04/07 00:00 [received]
PHST- 2019/09/23 00:00 [revised]
PHST- 2019/09/24 00:00 [accepted]
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2019/09/28 06:00 [entrez]
AID - S0014-2999(19)30647-8 [pii]
AID - 10.1016/j.ejphar.2019.172695 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Nov 15;863:172695. doi: 10.1016/j.ejphar.2019.172695. Epub 
      2019 Sep 24.