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rdf:type |
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lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0017262,
umls-concept:C0030685,
umls-concept:C0086282,
umls-concept:C0162638,
umls-concept:C0185117,
umls-concept:C0205217,
umls-concept:C0332281,
umls-concept:C0376515,
umls-concept:C0391871,
umls-concept:C0521451,
umls-concept:C0680255,
umls-concept:C1070653,
umls-concept:C1135922,
umls-concept:C1159966,
umls-concept:C1283071,
umls-concept:C1425143,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1963578,
umls-concept:C2911684
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pubmed:issue |
12
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pubmed:dateCreated |
2007-11-8
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pubmed:abstractText |
We have previously shown that when skeletal myoblasts are cultured in differentiation medium (DM), roughly 30% undergo caspase 3-dependent apoptosis rather than differentiation. Herein, we investigate the molecular mechanism responsible for the activation of caspase 3 and the ensuing apoptosis. When 23A2 myoblasts are cultured in DM, caspase 9 activity is increased and pharmacological abrogation of caspase 9 activation impairs caspase 3 activation and apoptosis. Further, we detect a time dependent release of mitochondrial cytochrome C into the cytosol in roughly 30% of myoblasts. Inclusion of cycloheximide inhibits the release of cytochrome C, the activation of caspase 9 and apoptosis. These data indicate that the mitochondrial pathway plays a role in this apoptotic process and that engagement of this pathway relies on de novo protein synthesis. Through RT-PCR and immunoblot analysis, we have determined that the expression level of the pro-apoptotic Bcl2 family member PUMA is elevated when 23A2 myoblasts are cultured in DM. Further, silencing of PUMA inhibits the release of cytochrome C and apoptosis. Signaling by the transcription factor p53 is not responsible for the increased level of PUMA. Finally, myoblasts rescued from apoptosis by either inhibition of elevated caspase 9 activity or silencing of PUMA are competent for differentiation. These results indicate a critical role for PUMA in the apoptosis associated with skeletal myoblast differentiation and that a p53-independent mechanism is responsible for the increased expression of PUMA in these cells.
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pubmed:grant |
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Benzothiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/PUMA protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Toluene,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/pifithrin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1360-8185
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2143-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17879164-Animals,
pubmed-meshheading:17879164-Apoptosis,
pubmed-meshheading:17879164-Apoptosis Regulatory Proteins,
pubmed-meshheading:17879164-Benzothiazoles,
pubmed-meshheading:17879164-Caspase 3,
pubmed-meshheading:17879164-Caspase 9,
pubmed-meshheading:17879164-Cell Differentiation,
pubmed-meshheading:17879164-Culture Media,
pubmed-meshheading:17879164-Cytochromes c,
pubmed-meshheading:17879164-DNA Fragmentation,
pubmed-meshheading:17879164-Enzyme Activation,
pubmed-meshheading:17879164-Mice,
pubmed-meshheading:17879164-Mitochondria,
pubmed-meshheading:17879164-Myoblasts, Skeletal,
pubmed-meshheading:17879164-Protein Biosynthesis,
pubmed-meshheading:17879164-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17879164-Toluene,
pubmed-meshheading:17879164-Tumor Suppressor Protein p53,
pubmed-meshheading:17879164-Tumor Suppressor Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
Increased expression of the pro-apoptotic Bcl2 family member PUMA is required for mitochondrial release of cytochrome C and the apoptosis associated with skeletal myoblast differentiation.
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pubmed:affiliation |
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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