PMID- 10362772
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20220410
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 6
DP  - 1999 Jun
TI  - Partial ATP depletion induces Fas- and caspase-mediated apoptosis in MDCK cells.
PG  - F837-46
LID - 10.1152/ajprenal.1999.276.6.F837 [doi]
AB  - Brief periods of in vitro hypoxia/ischemia induce apoptosis of cultured renal 
      epithelial cells, but the underlying mechanisms remain unknown. We show that 
      partial ATP depletion (approximately 10-65% of control) results in a 
      duration-dependent induction of apoptosis in Madin-Darby canine kidney (MDCK) 
      cells, as evidenced by internucleosomal DNA cleavage (DNA laddering and in situ 
      nick end labeling), morphological changes (cell shrinkage), and plasma membrane 
      alterations (externalization of phosphatidylserine). The ATP-depleted cells 
      display a significant upregulation of Fas, Fas ligand, and the Fas-associating 
      protein with death domain (FADD). Exogenous application of stimulatory Fas 
      monoclonal antibodies also induces apoptosis in nonischemic MDCK cells, 
      indicating that they retain Fas-dependent pathways of programmed cell death. 
      Furthermore, cleavage of poly(ADP)ribose polymerase (PARP) is evident after ATP 
      depletion, indicating activation of caspases. Indeed, the apoptotic cells display 
      a significant increase in caspase-8 (FLICE) activity. Finally, apoptosis induced 
      by ATP depletion is ameliorated by pretreatment with inhibitors of caspase-8 
      (IETD), caspase-1 (YVAD), or caspase-3 (DEVD) but is not affected by inhibitors 
      of serine proteases (TPCK). Our results indicate that partial ATP depletion of 
      MDCK cells results in apoptosis and that Fas- and caspase-mediated pathways may 
      play a critical role.
FAU - Feldenberg, L R
AU  - Feldenberg LR
AD  - Division of Pediatric Nephrology, Yale University School of Medicine, New Haven, 
      Connecticut 06520, USA.
FAU - Thevananther, S
AU  - Thevananther S
FAU - del Rio, M
AU  - del Rio M
FAU - de Leon, M
AU  - de Leon M
FAU - Devarajan, P
AU  - Devarajan P
LA  - eng
GR  - DK-47072/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (fas Receptor)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Adenosine Triphosphate/*deficiency
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Carrier Proteins/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspase Inhibitors
MH  - Caspases/metabolism/*physiology
MH  - Cell Line
MH  - Dogs
MH  - Enzyme Inhibitors/pharmacology
MH  - Fas Ligand Protein
MH  - Fas-Associated Death Domain Protein
MH  - Intracellular Membranes/metabolism
MH  - Kidney/cytology/metabolism/*physiology
MH  - Membrane Glycoproteins/metabolism
MH  - Poly(ADP-ribose) Polymerases/chemistry
MH  - Time Factors
MH  - fas Receptor/*physiology
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1152/ajprenal.1999.276.6.F837 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Jun;276(6):F837-46. doi: 10.1152/ajprenal.1999.276.6.F837.