Source:http://linkedlifedata.com/resource/pubmed/id/11222638
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2001-3-6
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| pubmed:abstractText |
In studies of transgenic (Tg) mice that overexpress insulin-like growth factor-I (IGF-I) exclusively in the CNS, we demonstrated a dramatic increase in cerebellar granule cell number that appeared to be attributable predominantly to enhanced survival. IGF-I anti-apoptotic actions are well established in cultured neurons, but comparable studies in vivo are few. Using the same Tg mice, therefore, we set out to document IGF-I anti-apoptotic effects during cerebellar development and to probe IGF-I signaling mechanisms. Compared with cerebella (CBs) of non-Tg littermates, those of Tg mice had fewer apoptotic cells at postnatal day 7 (P7) and showed a similar tendency at P14 and P21. At each age studied, procaspase-3 and caspase-3 were decreased in CBs of Tg mice. The caspase-3 decline was accompanied by decreases in the 85 kDa fragment of Poly(ADP-ribose) polymerase, a known product of caspase cleavage, suggesting decreased caspase activity. At P7 decreased apoptosis in Tg mice was associated with increased expression of the anti-apoptotic Bcl genes, Bcl-x(L) and Bcl-2. The mRNA expression of the proapoptotic Bcl genes, Bax and Bad, also was increased, but no changes were observed in the abundance of their proteins. At P14 Bcl-xL and Bcl-2 expression were similar in normal and Tg mice; Bax mRNA was unchanged in Tg mice, but its protein abundance was decreased, and both Bad mRNA and protein abundance were decreased. At P21 Bcl-xL and Bcl-2 expression were unchanged, but Bax and Bad expression were decreased. Our data show that IGF-I exerts anti-apoptotic actions during cerebellar development, and thereby alters the magnitude of naturally occurring apoptosis. IGF-I appears to affect multiple steps in the apoptotic pathway in a developmentally specific manner. IGF-I decreases caspase-3 availability and activity, increases the expression of anti-apoptotic Bcl-x(L) and Bcl-2 during early postnatal development, and decreases proapoptotic Bax and Bad expression at later developmental stages.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1481-9
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11222638-Aging,
pubmed-meshheading:11222638-Animals,
pubmed-meshheading:11222638-Apoptosis,
pubmed-meshheading:11222638-Carrier Proteins,
pubmed-meshheading:11222638-Caspase 3,
pubmed-meshheading:11222638-Caspases,
pubmed-meshheading:11222638-Cerebellum,
pubmed-meshheading:11222638-Enzyme Precursors,
pubmed-meshheading:11222638-Gene Expression Regulation, Developmental,
pubmed-meshheading:11222638-Insulin-Like Growth Factor I,
pubmed-meshheading:11222638-Mice,
pubmed-meshheading:11222638-Mice, Transgenic,
pubmed-meshheading:11222638-Nervous System Malformations,
pubmed-meshheading:11222638-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:11222638-Proto-Oncogene Proteins,
pubmed-meshheading:11222638-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11222638-RNA, Messenger,
pubmed-meshheading:11222638-Signal Transduction,
pubmed-meshheading:11222638-bcl-2-Associated X Protein,
pubmed-meshheading:11222638-bcl-Associated Death Protein,
pubmed-meshheading:11222638-bcl-X Protein
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| pubmed:year |
2001
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| pubmed:articleTitle |
Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by altering the expression of Bcl family proteins in a developmentally specific manner.
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| pubmed:affiliation |
Department of Pediatrics, The University of North Carolina, Chapel Hill, North Carolina 27599-7220, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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