PMID- 15579135
OWN - NLM
STAT- MEDLINE
DCOM- 20060407
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 387
IP  - Pt 3
DP  - 2005 May 1
TI  - Role of compartmentalized redox-active iron in hydrogen peroxide-induced DNA 
      damage and apoptosis.
PG  - 703-10
AB  - Jurkat cells in culture were exposed to oxidative stress in the form of 
      continuously generated hydrogen peroxide, obtained by the addition of glucose 
      oxidase to the medium. This treatment induced a rapid, dose-dependent increase in 
      the ICIP (intracellular calcein-chelatable iron pool). Early destabilization of 
      lysosomal membranes and subsequent nuclear DNA strand breaks were also observed, 
      as evaluated by the Acridine Orange relocation test and the comet assay 
      respectively. Somewhat later, these effects were followed by a lowered 
      mitochondrial membrane potential, with release of cytochrome c and 
      apoptosis-inducing factor. These events were all prevented if cells were 
      pretreated with the potent iron chelator DFO (desferrioxamine) for a period of 
      time (2-3 h) long enough to allow the drug to reach the lysosomal compartment 
      following fluid-phase endocytosis. The hydrophilic calcein, a cleavage product of 
      calcein acetoxymethyl ester following the action of cytosolic esterases, 
      obviously does not penetrate intact lysosomal membranes, thus explaining why ICIP 
      increased dramatically following lysosomal rupture. The rapid decrease in ICIP 
      after addition of DFO to the medium suggests draining of cytosolic iron to the 
      medium, rather than penetration of DFO through the plasma membrane. Most 
      importantly, these observations directly connect oxidative stress and resultant 
      DNA damage with lysosomal rupture and the release of redox-active iron into the 
      cytosol and, apparently, the nucleus.
FAU - Tenopoulou, Margarita
AU  - Tenopoulou M
AD  - Laboratory of Biological Chemistry, University of Ioannina Medical School, 451 10 
      Ioannina, Greece.
FAU - Doulias, Paschalis-Thomas
AU  - Doulias PT
FAU - Barbouti, Alexandra
AU  - Barbouti A
FAU - Brunk, Ulf
AU  - Brunk U
FAU - Galaris, Dimitrios
AU  - Galaris D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Fluoresceins)
RN  - 0 (Iron Chelating Agents)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E1UOL152H7 (Iron)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - V0YM2B16TS (fluorexon)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Cell Membrane/physiology
MH  - DNA Damage/*physiology
MH  - Deferoxamine/pharmacology
MH  - Fluoresceins/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Iron/*physiology
MH  - Iron Chelating Agents/*pharmacology
MH  - Jurkat Cells
MH  - Lysosomes/physiology
MH  - Membrane Potentials/physiology
MH  - Mitochondria/physiology
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Temperature
MH  - Time
PMC - PMC1135000
EDAT- 2004/12/08 09:00
MHDA- 2006/04/08 09:00
PMCR- 2005/11/01
CRDT- 2004/12/08 09:00
PHST- 2004/12/08 09:00 [pubmed]
PHST- 2006/04/08 09:00 [medline]
PHST- 2004/12/08 09:00 [entrez]
PHST- 2005/11/01 00:00 [pmc-release]
AID - BJ20041650 [pii]
AID - bj3870703 [pii]
AID - 10.1042/BJ20041650 [doi]
PST - ppublish
SO  - Biochem J. 2005 May 1;387(Pt 3):703-10. doi: 10.1042/BJ20041650.