PMID- 10532637
OWN - NLM
STAT- MEDLINE
DCOM- 19991029
LR  - 20120622
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - Survival- and death-promoting events after transient cerebral ischemia:
      phosphorylation of Akt, release of cytochrome C and Activation of caspase-like
      proteases.
PG  - 1126-35
AB  - Release of cytochrome c (cyt c) into cytoplasm initiates caspase-mediated
      apoptosis, whereas activation of Akt kinase by phosphorylation at serine-473
      prevents apoptosis in several cell systems. To investigate cell death and cell
      survival pathways, the authors studied release of cyt c, activation of caspase,
      and changes in Akt phosphorylation in rat brains subjected to 15 minutes of
      ischemia followed by varying periods of reperfusion. The authors found by
      electron microscopic study that a portion of mitochondria was swollen and
      structurally altered, whereas the cell membrane and nuclei were intact in
      hippocampal CA1 neurons after 36 hours of reperfusion. In some neurons, the
      pattern of immunostaining for cyt c changed from a punctuate pattern, likely
      representing mitochondria, to a more diffuse cytoplasmic localization at 36 and
      48 hours of reperfusion as examined by laser-scanning confocal microscopic study.
      Western blot analysis showed that cyt c was increased in the cytosolic fraction
      in the hippocampus after 36 and 48 hours of reperfusion. Consistently,
      caspase-3-like activity was increased in these hippocampal samples. As
      demonstrated by Western blot using phosphospecific Akt antibody, phosphorylation 
      of Akt at serine-473 in the hippocampal region was highly increased during the
      first 24 hours but not at 48 hours of reperfusion. The authors conclude that
      transient cerebral ischemia activates both cell death and cell survival pathways 
      after ischemia. The activation of Akt during the first 24 hours conceivably may
      be one of the factors responsible for the delay in neuronal death after global
      ischemia.
FAU - Ouyang, Y B
AU  - Ouyang YB
AD  - Laboratory of Neurochemistry, Center for the Study of Neurological Disease, The
      Queen's Medical Center, Honolulu, Hawaii 96813, USA.
FAU - Tan, Y
AU  - Tan Y
FAU - Comb, M
AU  - Comb M
FAU - Liu, C L
AU  - Liu CL
FAU - Martone, M E
AU  - Martone ME
FAU - Siesjo, B K
AU  - Siesjo BK
FAU - Hu, B R
AU  - Hu BR
LA  - eng
GR  - NS07838/NS/NINDS NIH HHS/United States
GR  - NS36810/NS/NINDS NIH HHS/United States
GR  - RR04050/RR/NCRR 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  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin)
RN  - 0 (Coumarins)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Oligopeptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (acetyl-aspartyl-glutamyl-valyl-aspartal)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain/blood supply/enzymology/pathology
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - Cell Death/physiology
MH  - Cell Survival/physiology
MH  - Coumarins/pharmacology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Cytochrome c Group/analysis/*metabolism
MH  - Cytosol/enzymology
MH  - Electron Transport Complex IV/analysis/metabolism
MH  - Enzyme Activation/physiology
MH  - Ischemic Attack, Transient/*metabolism/*pathology
MH  - Male
MH  - Microscopy, Electron
MH  - Mitochondria/enzymology
MH  - Oligopeptides/pharmacology
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/analysis/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-akt
MH  - Pyramidal Cells/chemistry/enzymology/ultrastructure
MH  - Rats
MH  - Rats, Wistar
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1097/00004647-199910000-00009 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 1999 Oct;19(10):1126-35. doi:
      10.1097/00004647-199910000-00009.