PMID- 15368542
OWN - NLM
STAT- MEDLINE
DCOM- 20050421
LR  - 20210109
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 203
IP  - 1
DP  - 2005 Apr
TI  - Regulation of Fas (CD95)-induced apoptotic and necrotic cell death by reactive 
      oxygen species in macrophages.
PG  - 78-84
AB  - Although reactive oxygen species (ROS) have long been suspected to play a key 
      role in Fas (CD95)-induced cell death, the identity of specific ROS involved in 
      this process and the relationship between apoptotic and necrotic cell death 
      induced by Fas are largely unknown. Using electron spin resonance (ESR) 
      spectroscopy, we showed that activation of Fas receptor by its ligand (FasL) in 
      macrophages resulted in a rapid and transient production of hydrogen peroxide 
      (H2O2) and hydroxyl radicals (*OH). The response was visible as early as 5 min 
      and peaked at approximately 45 min post-treatment. Morphological analysis of 
      total death response (apoptosis vs. necrosis) showed dose and time dependency 
      with apoptosis significantly increased at 6 h after the treatment, while necrosis 
      remained at a baseline level. Only at a 35-fold increase in apoptosis did 
      necrosis become significant. Inhibition of apoptosis by a pan-caspase inhibitor, 
      benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD-fmk), significantly 
      inhibited cell necrosis, indicating the linkage between the two events. Catalase 
      (H2O2 scavenger) and deferoxamine (*OH scavenger) effectively inhibited the total 
      death response as well as the ESR signals, while superoxide dismutase (SOD) (O2*- 
      scavenger) had minimal effects. These results established the role for H2O2 and 
      *OH as key participants in Fas-induced cell death and indicated apoptosis as a 
      primary mode of cell death preceding necrosis. Because the Fas death pathway is 
      implicated in various inflammatory and immunologic disorders, utilization of 
      antioxidants and apoptosis inhibitors as potential therapeutic agents may be 
      advantageous.
CI  - 2004 Wiley-Liss, Inc.
FAU - Medan, Djordje
AU  - Medan D
AD  - Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West 
      Virginia 26506, USA.
FAU - Wang, Liying
AU  - Wang L
FAU - Toledo, David
AU  - Toledo D
FAU - Lu, Bin
AU  - Lu B
FAU - Stehlik, Christian
AU  - Stehlik C
FAU - Jiang, Bing-Hua
AU  - Jiang BH
FAU - Shi, Xianglin
AU  - Shi X
FAU - Rojanasakul, Yon
AU  - Rojanasakul Y
LA  - eng
GR  - HL071545/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (fas Receptor)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Cell Line
MH  - Electron Spin Resonance Spectroscopy
MH  - Fas Ligand Protein
MH  - Hydrogen Peroxide/metabolism
MH  - Macrophages/*cytology/*metabolism
MH  - Membrane Glycoproteins/pharmacology
MH  - Mice
MH  - Necrosis/immunology/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - fas Receptor/*metabolism
EDAT- 2004/09/16 05:00
MHDA- 2005/04/22 09:00
CRDT- 2004/09/16 05:00
PHST- 2004/09/16 05:00 [pubmed]
PHST- 2005/04/22 09:00 [medline]
PHST- 2004/09/16 05:00 [entrez]
AID - 10.1002/jcp.20201 [doi]
PST - ppublish
SO  - J Cell Physiol. 2005 Apr;203(1):78-84. doi: 10.1002/jcp.20201.