PMID- 20547138
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1797
IP  - 10
DP  - 2010 Oct
TI  - Glutaredoxin 2 prevents H(2)O(2)-induced cell apoptosis by protecting complex I 
      activity in the mitochondria.
PG  - 1705-15
LID - 10.1016/j.bbabio.2010.06.003 [doi]
AB  - Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of 
      glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not 
      well understood. The purpose of this study is to evaluate the potential 
      anti-apoptotic function of Grx2 by examining its ability to protect complex I in 
      the mitochondrial electron transport system using human lens epithelial cells as 
      a model. We found that cells treated with 200muM hydrogen peroxide (H(2)O(2)) for 
      24h exhibited decreased viability and became apoptotic with corresponding Bax 
      up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial 
      cytochrome c leakage. Grx2 over-expression (OE) could protect cells against 
      H(2)O(2)-induced damage while Grx2 knockdown (KD) showed the opposite effect. 
      Under the same conditions, H(2)O(2) treatment caused 50% inactivation of complex 
      I activity in control cells (vector only), 75% in Grx2 KD cells but only 20% in 
      Grx2 OE cells. Furthermore, the inactivated complex I in the H(2)O(2)-treated 
      cells could be protected mostly by importing the purified nascent Grx2 protein, 
      but not the Grx2 protein mutated at the active site with C70S, or C73S, or with 
      C70S plus C73S. Immunoprecipitation study also revealed that Grx2 co-precipitated 
      with complex I, but not complex II, in the mitochondrial lysate. Thus, the 
      mechanism of Grx2 protection against H(2)O(2)-induced apoptosis is likely 
      associated with its ability to preserve complex I.
CI  - Published by Elsevier B.V.
FAU - Wu, Hongli
AU  - Wu H
AD  - Departement of Veterinary and Biomedical Sciences, University of 
      Nebraska-Lincoln, Lincoln, NE 68583, USA.
FAU - Xing, Kuiyi
AU  - Xing K
FAU - Lou, Marjorie F
AU  - Lou MF
LA  - eng
GR  - R01 EY010595/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100612
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Glutaredoxins)
RN  - 0 (Oxidants)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Electron Transport Complex I/*metabolism
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Glutaredoxins/genetics/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Immunoprecipitation
MH  - Lens, Crystalline/cytology
MH  - Mitochondria/*metabolism
MH  - Mutation
MH  - Oxidants/pharmacology
MH  - Protein Binding
MH  - RNA Interference
PMC - PMC2964346
MID - NIHMS213614
EDAT- 2010/06/16 06:00
MHDA- 2010/10/29 06:00
PMCR- 2011/10/01
CRDT- 2010/06/16 06:00
PHST- 2010/01/25 00:00 [received]
PHST- 2010/05/29 00:00 [revised]
PHST- 2010/06/07 00:00 [accepted]
PHST- 2010/06/16 06:00 [entrez]
PHST- 2010/06/16 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - S0005-2728(10)00626-2 [pii]
AID - 10.1016/j.bbabio.2010.06.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2010 Oct;1797(10):1705-15. doi: 
      10.1016/j.bbabio.2010.06.003. Epub 2010 Jun 12.