Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: EC:3.4.22.60 (
caspase-7
)
920
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Caspase-7 is an executioner caspase that plays a key role in apoptosis, cancer, and a number of neurodegenerative diseases. The mechanism of
caspase-7
activation by granzyme B and caspase-3 has been well characterized. However, whether other proteases such as calpains activate or inactivate
caspase-7
is not known. Here, we present that recombinant
caspase-7
is directly cleaved by
calpain-1
within the large subunit of
caspase-7
to produce two novel products, large subunit p18 and p17. This new form of
caspase-7
has a 6-fold increase in V(max) when compared with the previously characterized p20/p12 form. Zymography revealed that the smaller
caspase-7
product (p17) is 18-fold more active than either the caspase-3-cleaved product (p20) or the larger
calpain-1
product of
caspase-7
(p18). Mass spectrometry and site-directed mutagenesis identified the calpain cleavage sites within the
caspase-7
large subunit at amino acid 36 and 45/47. These proteolysis events occur in vivo as indicated by the accumulation of
caspase-7
p18 and p17 subunits in cortical neurons undergoing Ca(2+) dysregulation. Further, cleavage at amino acid 45/47 of
caspase-7
by calpain results in a reduction in nuclear localization when compared with the caspase-3 cleavage product of
caspase-7
(p20). Our studies suggest the calpain-activated form of
caspase-7
has unique enzymatic activity, localization, and binding affinity when compared with the caspase-activated form.
...
PMID:Calpain-1 cleaves and activates caspase-7. 1961 26
Although L-glutamate is the main excitatory neurotransmitter in the retina, excess glutamate level triggers severe neuronal damages. Therefore, monosodium glutamate has been used to probe neurodegenerative mechanisms but precise toxicity schedule is not available in vivo. We report, for the first time, a temporal analysis of apoptotic processes induced by subcutaneously applied monosodium glutamate. We investigated the glutamate triggered subcellular processes over a time scale of 48 h in neonatal retina. We employed immunoblots to measure the level of activated apoptotic factors and immunocytochemistry to reveal the dying cells. Upregulation of active caspase-9 started at 3 h and peaked at 6 h post-injection. Activations of caspase-3, caspase-6 and
caspase-7
consistent with their late-phase roles increased at 6 h post-injection. The apoptotic processes were terminated by 24 h post-injection. Caspase 12 and calpain-2 seemed unaffected by subcutaneous monosodium glutamate administration. Uniquely, we found that the ubiquitous
calpain-1
is not expressed in newborn rat retina.
...
PMID:A precise temporal dissection of monosodium glutamate-induced apoptotic events in newborn rat retina in vivo. 2151 46
