PMID- 27130034
OWN - NLM
STAT- MEDLINE
DCOM- 20180109
LR  - 20180111
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 96
DP  - 2016 Jul
TI  - Iron-sulfur cluster damage by the superoxide radical in neural tissues of the 
      SOD1(G93A) ALS rat model.
PG  - 313-22
LID - S0891-5849(16)30046-6 [pii]
LID - 10.1016/j.freeradbiomed.2016.04.028 [doi]
AB  - Extensive clinical investigations, in hand with biochemical and biophysical 
      research, have associated brain iron accumulation with the pathogenesis of the 
      amyotrophic lateral sclerosis (ALS) disease. The origin of iron is still not 
      identified, but it is proposed that it forms redox active complexes that can 
      participate in the Fenton reaction generating the toxic hydroxyl radical. In this 
      paper, the state of iron in the neural tissues isolated from SOD1(G93A) 
      transgenic rats was investigated using low temperature EPR spectroscopy and is 
      compared with that of nontransgenic (NTg) littermates. The results showed that 
      iron in neural tissues is present as high- and low-spin, heme and non-heme iron. 
      It appears that the SOD1(G93A) rat neural tissues were most likely exposed in 
      vivo to higher amounts of reactive oxygen species when compared to the 
      corresponding NTg tissues, as they showed increased oxidized [3Fe-4S](1+) cluster 
      content relative to [4Fe-4S](1+). Also, the activity of cytochrome c oxidase 
      (CcO) was found to be reduced in these tissues, which may be associated with the 
      observed uncoupling of heme a3 Fe and CuB in the O2-reduction site of the enzyme. 
      Furthermore, the SOD1(G93A) rat spinal cords and brainstems contained more 
      manganese, presumably from MnSOD, than those of NTg rats. The addition of 
      potassium superoxide to all neural tissues ex vivo, led to the [4Fe-4S]-->[3Fe-4S] 
      cluster conversion and concurrent release of Fe. These results suggest that the 
      superoxide anion may be the cause of the observed oxidative damage to SOD1(G93A) 
      rat neural tissues and that the iron-sulfur clusters may be the source of poorly 
      liganded redox active iron implicated in ALS pathogenesis. Low temperature EPR 
      spectroscopy appears to be a valuable tool in assessing the role of metals in 
      neurodegenerative diseases.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Popovic-Bijelic, Ana
AU  - Popovic-Bijelic A
AD  - University of Belgrade - Faculty of Physical Chemistry, EPR Laboratory, 
      Studentski trg 12-16, 11158 Belgrade, Serbia. Electronic address: 
      ana@ffh.bg.ac.rs.
FAU - Mojovic, Milos
AU  - Mojovic M
AD  - University of Belgrade - Faculty of Physical Chemistry, EPR Laboratory, 
      Studentski trg 12-16, 11158 Belgrade, Serbia.
FAU - Stamenkovic, Stefan
AU  - Stamenkovic S
AD  - University of Belgrade - Faculty of Biology, Center for Laser Microscopy, 
      Studentski trg 3, 11158 Belgrade, Serbia.
FAU - Jovanovic, Milos
AU  - Jovanovic M
AD  - University of Belgrade - Faculty of Biology, Center for Laser Microscopy, 
      Studentski trg 3, 11158 Belgrade, Serbia.
FAU - Selakovic, Vesna
AU  - Selakovic V
AD  - Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 
      Belgrade, Serbia.
FAU - Andjus, Pavle
AU  - Andjus P
AD  - University of Belgrade - Faculty of Biology, Center for Laser Microscopy, 
      Studentski trg 3, 11158 Belgrade, Serbia.
FAU - Bacic, Goran
AU  - Bacic G
AD  - University of Belgrade - Faculty of Physical Chemistry, EPR Laboratory, 
      Studentski trg 12-16, 11158 Belgrade, Serbia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160427
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 11062-77-4 (Superoxides)
RN  - 42VZT0U6YR (Heme)
RN  - 70FD1KFU70 (Sulfur)
RN  - E1UOL152H7 (Iron)
RN  - EC 1.15.1.1 (Sod1 protein, rat)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/*genetics/metabolism/pathology
MH  - Animals
MH  - Electron Spin Resonance Spectroscopy
MH  - Electron Transport Complex IV/metabolism
MH  - Heme/chemistry/genetics
MH  - Humans
MH  - Iron/chemistry/*metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*genetics
MH  - Rats
MH  - Rats, Transgenic
MH  - Sulfur/chemistry
MH  - Superoxide Dismutase-1/*genetics/metabolism
MH  - Superoxides/toxicity
OTO - NOTNLM
OT  - ALS
OT  - EPR
OT  - Fe-S cluster
OT  - SOD1(G93A)
OT  - Superoxide radical
EDAT- 2016/05/01 06:00
MHDA- 2018/01/10 06:00
CRDT- 2016/05/01 06:00
PHST- 2015/10/17 00:00 [received]
PHST- 2016/04/22 00:00 [revised]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/05/01 06:00 [entrez]
PHST- 2016/05/01 06:00 [pubmed]
PHST- 2018/01/10 06:00 [medline]
AID - S0891-5849(16)30046-6 [pii]
AID - 10.1016/j.freeradbiomed.2016.04.028 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2016 Jul;96:313-22. doi: 
      10.1016/j.freeradbiomed.2016.04.028. Epub 2016 Apr 27.