PMID- 10777562
OWN - NLM
STAT- MEDLINE
DCOM- 20000602
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 17
DP  - 2000 Apr 28
TI  - Selective involvement of superoxide anion, but not downstream compounds hydrogen 
      peroxide and peroxynitrite, in tumor necrosis factor-alpha-induced apoptosis of 
      rat mesangial cells.
PG  - 12684-91
AB  - Tumor necrosis factor-alpha (TNF-alpha) induces reactive oxygen species (ROS) 
      that serve as second messengers for intracellular signaling. Currently, precise 
      roles of individual ROS in the actions of TNF-alpha remain to be elucidated. In 
      this report, we investigated the roles of superoxide anion (O-(2)), hydrogen 
      peroxide (H(2)O(2)), and peroxynitrite (ONOO(-)) in TNF-alpha-triggered apoptosis 
      of mesangial cells. Mesangial cells stimulated by TNF-alpha produced O-(2) and 
      underwent apoptosis. The apoptosis was inhibited by transfection with manganese 
      superoxide dismutase or treatment with a pharmacological scavenger of O-(2), 
      Tiron. In contrast, although exogenous H(2)O(2) induced apoptosis, 
      TNF-alpha-triggered apoptosis was not affected either by transfection with 
      catalase cDNA or by treatment with catalase protein or glutathione ethyl ester. 
      Similarly, although ONOO(-) precursor SIN-1 induced apoptosis, treatment with a 
      scavenger of ONOO(-), uric acid, or an inhibitor of nitric oxide synthesis, 
      N(G)-nitro-L-argininemethyl ester hydrochloride, did not affect the 
      TNF-alpha-triggered apoptosis. Like TNF-alpha-induced apoptosis, treatment with a 
      O-(2)-releasing agent, pyrogallol, induced typical apoptosis even in the 
      concurrent presence of scavengers for H(2)O(2) and ONOO(-). These results 
      suggested that, in mesangial cells, TNF-alpha induces apoptosis through selective 
      ROS. O-(2), but not H(2)O(2) or ONOO(-), was identified as the crucial mediator 
      for the TNF-alpha-initiated, apoptotic pathway.
FAU - Moreno-Manzano, V
AU  - Moreno-Manzano V
AD  - Department of Medicine, University College Medical School, University College 
      London, The Rayne Institute, London WC1E 6JJ, United Kingdom.
FAU - Ishikawa, Y
AU  - Ishikawa Y
FAU - Lucio-Cazana, J
AU  - Lucio-Cazana J
FAU - Kitamura, M
AU  - Kitamura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 26404-66-0 (peroxynitric acid)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Glomerular Mesangium/*pathology
MH  - Humans
MH  - Hydrogen Peroxide/*metabolism
MH  - Male
MH  - Microscopy, Fluorescence
MH  - NF-kappa B/metabolism
MH  - Nitrates/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
MH  - Superoxides/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/04/25 09:00
MHDA- 2000/06/10 09:00
CRDT- 2000/04/25 09:00
PHST- 2000/04/25 09:00 [pubmed]
PHST- 2000/06/10 09:00 [medline]
PHST- 2000/04/25 09:00 [entrez]
AID - S0021-9258(19)83375-6 [pii]
AID - 10.1074/jbc.275.17.12684 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Apr 28;275(17):12684-91. doi: 10.1074/jbc.275.17.12684.