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)
Caspases are proteases involved in various physiological and pathological processes in the nervous system, including development and pathogenesis.
GRASP-1
is a recently identified neuronal substrate of caspase-3-subfamily caspases. It is a Ras-guanine nucleotide exchange factor (RasGEF) that interacts with the glutamate receptor interacting protein (GRIP). This alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor/GRIP protein complex has been proposed to be involved in AMPA receptor synaptic targeting. The caspase-3 cleavage of
GRASP-1
separates the N-terminal RasGEF catalytic domain from the C-terminal GRIP-interacting region, potentially disrupting regulation of the RasGEF activity by GRIP. To examine the regulation and regional distribution of the caspase-3 cleavage of
GRASP-1
in vivo, we generated a cleavage site-specific antibody, termed CGP, against the cleaved N-terminal fragment of
GRASP-1
. Using this antibody, we have examined the caspase cleavage of
GRASP-1
during postnatal development and following
ischemia
in mice. We found that caspase cleavage of
GRASP-1
occurs in specific brain regions in a time-dependent manner during development and
ischemia
. This data provides an important account of the brain areas that might require caspase-3 activity in postnatal development and ischemic damage, which has not been documented. It also demonstrates that the CGP antibody is a powerful tool for studying neuronal activity of the caspase-3-subfamily caspases in vivo.
...
PMID:Physiological and pathological caspase cleavage of the neuronal RasGEF GRASP-1 as detected using a cleavage site-specific antibody. 1220 67
