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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2000-12-12
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pubmed:abstractText |
Caspase-3 knockout mice exhibit thickening of the internal granule cell layer of the cerebellum. Concurrently, it has been shown that intracerebral injection of pituitary adenylate cyclase-activating polypeptide (PACAP) induces a transient increase of the thickness of the cerebellar cortex. In the present study, we have investigated the possible effect of PACAP on caspase activity in cultured cerebellar granule cells from 8-day-old rat. Incubation of granule neurons with PACAP for 24 h promoted cell survival and prevented DNA fragmentation. Exposure of cerebellar granule cells to the specific caspase-3 inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethylketone (Z-DEVD-FMK) for 24 h markedly enhanced cell survival and inhibited apoptotic cell death. Time-course studies revealed that PACAP causes a prolonged inhibition of caspase-3 activity without affecting caspase-1. Administration of graded concentrations of PACAP for 3 h induced a dose-dependent inhibition of caspase-3 activity. Incubation of granule cells with both dibutyryl-cAMP (dbcAMP) and phorbol 12-myristate 13-acetate (PMA) mimicked the inhibitory effect of PACAP on caspase-3. Cotreatment of cultured neurons with the protein kinase A inhibitor H89 and the protein kinase C inhibitor chelerythrine abrogated the effect of PACAP on caspase-3 activity. In contrast, the ERK kinase inhibitor U0126 did not affect the action of PACAP on caspase-3 activity. These data demonstrate that PACAP prevents cerebellar granule neurons from apoptotic cell death through a protein kinase A- and protein kinase C-dependent inhibition of caspase-3 activity.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adcyap1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoactive Intestinal Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/acetyl-aspartyl-glutamyl-valyl-aspar...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13390-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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