Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0022116 (
ischemia
)
91,303
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Using a focal cerebral ischemia model in rats, brain
ischemia
-induced changes in expression levels of mRNA and protein, and activities of
proprotein convertase 2
(
PC2
) in the cortex were examined. In situ hybridization analyses revealed a transient upregulation of the mRNA level for
PC2
at an early reperfusion hour, at which the level of
PC2
protein was also high as determined by immunocytochemistry and western blotting. When enzymatic activities of
PC2
were analyzed using a synthetic substrate, a significant decrease was observed at early reperfusion hours at which levels of
PC2
protein were still high. Also decreased at these reperfusion hours were tissue levels of dynorphin-A(1-8) (DYN-A(1-8)), a
PC2
substrate, as determined by radioimmunoassay. Further examination of
PC2
protein biosynthesis by metabolic labeling in cultured neuronal cells showed that in ischemic cells, the proteolytic processing of
PC2
was greatly attenuated. Finally, in mice, an intracerebroventricular administration of synthetic DYN-A(1-8) significantly reduced the extent of ischemic brain injury. In mice those lack an active
PC2
, exacerbated brain injury was observed after an otherwise non-lethal focal
ischemia
. We conclude that brain
ischemia
attenuates
PC2
and
PC2
-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury.
...
PMID:Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains. 1914 96
