PMID- 18256309
OWN - NLM
STAT- MEDLINE
DCOM- 20080613
LR  - 20220410
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 294
IP  - 4
DP  - 2008 Apr
TI  - Autophagy is associated with apoptosis in cisplatin injury to renal tubular 
      epithelial cells.
PG  - F777-87
LID - 10.1152/ajprenal.00590.2007 [doi]
AB  - Autophagy has emerged as another major "programmed" mechanism to control life and 
      death much like "programmed cell death" is for apoptosis in eukaryotes. We 
      examined the expression of autophagic proteins and formation of autophagosomes 
      during progression of cisplatin injury to renal tubular epithelial cells (RTEC). 
      Autophagy was detected as early as 2-4 h after cisplatin exposure as indicated by 
      induction of LC3-I, conversion of LC3-I to LC3-II protein, and upregulation of 
      Beclin 1 and Atg5, essential markers of autophagy. The appearance of 
      cisplatin-induced punctated staining of autophagosome-associated LC3-II upon 
      GFP-LC3 transfection in RTEC provided further evidence for autophagy. The 
      autophagy inhibitor 3-methyladenine blocked punctated staining of autophagosomes. 
      The staining of normal cells with acridine orange displayed green fluorescence 
      with cytoplasmic and nuclear components in normal cells but displayed 
      considerable red fluorescence in cisplatin-treated cells, suggesting formation of 
      numerous acidic autophagolysosomal vacuoles. Autophagy inhibitors LY294002 or 
      3-methyladenine or wortmannin inhibited the formation of autophagosomes but 
      induced apoptosis after 2-4 h of cisplatin treatment as indicated by caspase-3/7 
      and -6 activation, nuclear fragmentation, and cell death. This switch from 
      autophagy to apoptosis by autophagic inhibitors further suggests that the 
      preapoptotic lag phase after treatment with cisplatin is mediated by autophagy. 
      At later stages of cisplatin injury, apoptosis was also found to be associated 
      with autophagy, as autophagic inhibitors and inactivation of autophagy proteins 
      Beclin 1 and Atg5 enhanced activation of caspases and apoptosis. Our results 
      demonstrate that induction of autophagy mounts an adaptive response, suppresses 
      cisplatin-induced apoptosis, and prolongs survival of RTEC.
FAU - Yang, Cheng
AU  - Yang C
AD  - Department of Medicine, Central Arkansas Veterans Healthcare System and 
      University of Arkansasfor Medical Sciences, Little Rock, Arkansas 72205, USA.
FAU - Kaushal, Varsha
AU  - Kaushal V
FAU - Shah, Sudhir V
AU  - Shah SV
FAU - Kaushal, Gur P
AU  - Kaushal GP
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080206
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antineoplastic Agents)
RN  - 5142-23-4 (3-methyladenine)
RN  - EC 3.4.22.- (Caspases)
RN  - JAC85A2161 (Adenine)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/toxicity
MH  - Autophagy/*drug effects
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Cisplatin/*toxicity
MH  - Epithelial Cells/drug effects/*pathology
MH  - Kidney Tubules/drug effects/*pathology
MH  - LLC-PK1 Cells
MH  - Swine
EDAT- 2008/02/08 09:00
MHDA- 2008/06/14 09:00
CRDT- 2008/02/08 09:00
PHST- 2008/02/08 09:00 [pubmed]
PHST- 2008/06/14 09:00 [medline]
PHST- 2008/02/08 09:00 [entrez]
AID - 00590.2007 [pii]
AID - 10.1152/ajprenal.00590.2007 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2008 Apr;294(4):F777-87. doi: 
      10.1152/ajprenal.00590.2007. Epub 2008 Feb 6.