PMID- 11483302
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 105
IP  - 1
DP  - 2001
TI  - Nitric oxide is involved in ischemia-induced apoptosis in brain: a study in 
      neuronal nitric oxide synthase null mice.
PG  - 79-86
AB  - Nitric oxide can promote or inhibit apoptosis depending on the cell type and 
      coexisting metabolic or experimental conditions. We examined the impact of nitric 
      oxide on development of apoptosis 6, 24, and 72 h after permanent middle cerebral 
      artery occlusion in mutant mice that lack the ability to generate nitric oxide 
      from neuronal nitric oxide synthase. Adjacent coronal sections passing through 
      the anterior commissure were stained with hematoxylin and eosin or terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). 
      Immunoblotting was used to identify changes in the anti- and proapoptotic 
      proteins Bcl-2 and Bax, respectively. Activation of caspases was assessed by 
      appearance of actin cleavage products using a novel antiserum directed against 
      32-kDa actin fragment (fractin). In the neuronal nitric oxide synthase mutant 
      mouse, infarct size and TUNEL positive apoptotic neurons were reduced compared to 
      the wild-type controls. At 6 h, Bcl-2 levels in the ischemic hemisphere were 
      increased in mutants but decreased in the wild-type strain. Bax levels did not 
      change significantly. Caspase-mediated actin cleavage appeared in the ischemic 
      hemisphere at this time point, and was significantly less in mutant brains at 72 
      h compared to the wild-type. The reduction in the number of TUNEL and fractin 
      positive apoptotic cells appears far greater than anticipated based on the 
      smaller lesion size in mutant mice.Hence, from these data we suggest that a 
      deficiency in neuronal nitric oxide production slows the development of apoptotic 
      cell death after ischemic injury and is associated with preserved Bcl-2 levels 
      and delayed activation of effector caspases.
FAU - Elibol, B
AU  - Elibol B
AD  - Department of Neurology, Faculty of Medicine, and Institute of neurological 
      Sciences and Psychiatry, Hacettepe university, Ankara, Turkey.
FAU - Soylemezoglu, F
AU  - Soylemezoglu F
FAU - Unal, I
AU  - Unal I
FAU - Fujii, M
AU  - Fujii M
FAU - Hirt, L
AU  - Hirt L
FAU - Huang, P L
AU  - Huang PL
FAU - Moskowitz, M A
AU  - Moskowitz MA
FAU - Dalkara, T
AU  - Dalkara T
LA  - eng
GR  - 101NS37141-01/NS/NINDS NIH HHS/United States
GR  - NS10828/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Actins)
RN  - 0 (Bax protein, mouse)
RN  - 0 (Coloring Agents)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.22.- (Caspases)
RN  - TDQ283MPCW (Eosine Yellowish-(YS))
RN  - YKM8PY2Z55 (Hematoxylin)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Brain/*enzymology/pathology/physiopathology
MH  - Brain Ischemia/*enzymology/pathology/physiopathology
MH  - Caspases/metabolism
MH  - Coloring Agents/pharmacology
MH  - DNA Fragmentation/physiology
MH  - Eosine Yellowish-(YS)/pharmacokinetics
MH  - Female
MH  - Hematoxylin/pharmacokinetics
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*enzymology/pathology
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase/*metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - bcl-2-Associated X Protein
EDAT- 2001/08/03 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/08/03 10:00
PHST- 2001/08/03 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/08/03 10:00 [entrez]
AID - S0306-4522(01)00159-2 [pii]
AID - 10.1016/s0306-4522(01)00159-2 [doi]
PST - ppublish
SO  - Neuroscience. 2001;105(1):79-86. doi: 10.1016/s0306-4522(01)00159-2.