PMID- 20162100
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1662-6427 (Electronic)
IS  - 1662-6427 (Linking)
VI  - 2
DP  - 2010
TI  - Persistent mitochondrial damage by nitric oxide and its derivatives: 
      neuropathological implications.
PG  - 1
LID - 10.3389/neuro.14.001.2010 [doi]
LID - 1
AB  - Approximately 15 years ago we reported that cytochrome c oxidase (CcO) was 
      persistently inhibited as a consequence of endogenous induction and activation of 
      nitric oxide ((*)NO) synthase-2 (NOS2) in astrocytes. Furthermore, the reactive 
      nitrogen species implicated was peroxynitrite. In contrast to the reversible 
      inhibition by (*)NO, which occurs rapidly, in competition with O(2), and has 
      signaling regulatory implications, the irreversible CcO damage by peroxynitrite 
      is progressive in nature and follows and/or is accompanied by damage to other key 
      mitochondrial bioenergetic targets. In purified CcO it has been reported that the 
      irreversible inhibition occurs through a mechanism involving damage of the heme 
      a(3)-Cu(B) binuclear center leading to an increase in the K(m) for oxygen. 
      Astrocyte survival, as a consequence of peroxynitrite exposure, is preserved due 
      to their robust bioenergetic and antioxidant defense mechanisms. However, by 
      releasing peroxynitrite to the neighboring neurons, whose antioxidant defense 
      can, under certain conditions, be fragile, activated astrocytes trigger 
      bioenergetic stress leading to neuronal cell death. Thus, such irreversible 
      inhibition of CcO by peroxynitrite may be a plausible mechanism for the neuronal 
      death associated with neurodegenerative diseases, in which the activation of 
      astrocytes plays a crucial role.
FAU - Bolanos, Juan P
AU  - Bolanos JP
AD  - Department of Biochemistry and Molecular Biology, Institute of Neurosciences of 
      Castilla- Leon, University of Salamanca Salamanca, Spain.
FAU - Heales, Simon J R
AU  - Heales SJ
LA  - eng
PT  - Journal Article
DEP - 20100203
PL  - Switzerland
TA  - Front Neuroenergetics
JT  - Frontiers in neuroenergetics
JID - 101477960
PMC - PMC2822548
OTO - NOTNLM
OT  - astrocytes
OT  - cytochrome c oxidase
OT  - neurodegeneration
OT  - neurons
OT  - nitric oxide
OT  - peroxynitrite
EDAT- 2010/02/18 06:00
MHDA- 2010/02/18 06:01
PMCR- 2010/01/01
CRDT- 2010/02/18 06:00
PHST- 2009/12/09 00:00 [received]
PHST- 2010/01/18 00:00 [accepted]
PHST- 2010/02/18 06:00 [entrez]
PHST- 2010/02/18 06:00 [pubmed]
PHST- 2010/02/18 06:01 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - 10.3389/neuro.14.001.2010 [doi]
PST - epublish
SO  - Front Neuroenergetics. 2010 Feb 3;2:1. doi: 10.3389/neuro.14.001.2010. 
      eCollection 2010.