PMID- 18037245
OWN - NLM
STAT- MEDLINE
DCOM- 20080422
LR  - 20131121
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 151
IP  - 1
DP  - 2008 Jan 2
TI  - Suppression of the inducible form of nitric oxide synthase prior to traumatic 
      brain injury improves cytochrome c oxidase activity and normalizes cellular 
      energy levels.
PG  - 148-54
AB  - We have previously shown that the observed immediate increase in nitric oxide 
      (NO) plays a significant role in the control of the cerebral microcirculation 
      following traumatic brain injury (TBI). However, a second consequence of 
      increased NO production after TBI may be impaired mitochondrial function, due to 
      the fact that NO is a well-known inhibitor of cytochrome c oxidase (CcO). CcO is 
      a key enzyme of the mitochondrial oxidative phosphorylation (OxPhos) machinery, 
      which creates cellular energy in the form of ATP. NO competes with oxygen at the 
      heme a(3)-Cu(B) reaction center of CcO. We thus hypothesized that TBI triggers 
      inhibition of CcO, which would in turn lead to a decreased energy production by 
      OxPhos at a time of an elevated energy demand for tissue remodeling. Here we show 
      that TBI as induced by an acceleration weight drop model of diffuse brain injury 
      in rats leads to CcO inhibition and dramatically decreased ATP levels in brain 
      cortex. CcO inhibition can be partially restored by application of iNOS antisense 
      oligonucleotides prior to TBI, which leads to a normalization of ATP levels 
      similar to the controls. We propose that a lack of energy after TBI caused by 
      inhibition of CcO is an important aspect of trauma pathology.
FAU - Huttemann, M
AU  - Huttemann M
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, MI 48201, USA. mhuttema@med.wayne.edu
FAU - Lee, I
AU  - Lee I
FAU - Kreipke, C W
AU  - Kreipke CW
FAU - Petrov, T
AU  - Petrov T
LA  - eng
GR  - NS39860/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070920
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oligoribonucleotides, Antisense)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Brain/pathology
MH  - Brain Injuries/enzymology/*metabolism/pathology
MH  - Electron Transport Complex IV/*metabolism
MH  - Energy Metabolism/*physiology
MH  - Enzyme Inhibitors/*pharmacology
MH  - In Situ Hybridization
MH  - Male
MH  - Mitochondria/drug effects/enzymology
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase Type II/antagonists & inhibitors/*biosynthesis/physiology
MH  - Oligoribonucleotides, Antisense/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation/drug effects
EDAT- 2007/11/27 09:00
MHDA- 2008/04/23 09:00
CRDT- 2007/11/27 09:00
PHST- 2007/06/15 00:00 [received]
PHST- 2007/09/11 00:00 [revised]
PHST- 2007/10/11 00:00 [accepted]
PHST- 2007/11/27 09:00 [pubmed]
PHST- 2008/04/23 09:00 [medline]
PHST- 2007/11/27 09:00 [entrez]
AID - S0306-4522(07)01167-0 [pii]
AID - 10.1016/j.neuroscience.2007.09.029 [doi]
PST - ppublish
SO  - Neuroscience. 2008 Jan 2;151(1):148-54. doi: 10.1016/j.neuroscience.2007.09.029. 
      Epub 2007 Sep 20.