Source:http://linkedlifedata.com/resource/pubmed/id/20713550
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2010-10-20
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| pubmed:abstractText |
Thapsigargin is a specific inhibitor of the sarco/endoplasmic reticulum Ca(2+) ATPase of the endoplasmic reticulum. Here, we show that stimulation of human HaCaT keratinocytes with nanomolar concentrations of thapsigargin triggers expression of activating transcription factor (ATF) 3, a basic-region leucin zipper transcription factor. ATF3 expression was also up-regulated in thapsigargin-stimulated glioma cells, hepatoma cells, retinal pigment epithelial cells, and airway epithelial cells. Thapsigargin-induced up-regulation of ATF3 expression in keratinocytes was attenuated by BAPTA-acetoxymethyl ester or by expression of the Ca(2+)-binding protein parvalbumin in the cytosol of HaCaT cells but not by a panel of pharmacological agents that chelate extracellular Ca(2+) (EGTA) or inhibit either ryanodine receptors (dantrolene) or voltage-gated Ca(2+) channels (nifedipine). Hence, elevated levels of intracellular Ca(2+), released from intracellular stores, are essential for the effect of thapsigargin on the biosynthesis of ATF3. The thapsigargin-induced signaling pathway was blocked by expression of either mitogen-activated protein kinase phosphatase-1 or -5. Experiments involving pharmacological and genetic tools revealed the importance of c-Jun N-terminal protein kinase (JNK) within the signaling cascade, whereas inhibition of extracellular signal-regulated protein kinase or p38 protein kinase did not attenuate thapsigargin-induced expression of ATF3. Functional studies showed that treatment of HaCaT keratinocytes with thapsigargin led to a 2-fold induction of caspase-3/7 activity. The up-regulation of caspase-3/7 activity in thapsigargin-stimulated HaCaT cells was attenuated by inhibition of JNK. Together, these data show that stimulation of HaCaT cells with thapsigargin induces a specific signaling pathway in keratinocytes involving activation of JNK, biosynthesis of ATF3, and up-regulation of caspase-3/7 activity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Anisomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Cations, Divalent,
http://linkedlifedata.com/resource/pubmed/chemical/DUSP10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Dual-Specificity Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1521-0111
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
78
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
865-76
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| pubmed:meshHeading |
pubmed-meshheading:20713550-Activating Transcription Factor 1,
pubmed-meshheading:20713550-Anisomycin,
pubmed-meshheading:20713550-Apoptosis,
pubmed-meshheading:20713550-Calcium,
pubmed-meshheading:20713550-Calcium-Transporting ATPases,
pubmed-meshheading:20713550-Caspase 3,
pubmed-meshheading:20713550-Caspase 7,
pubmed-meshheading:20713550-Cations, Divalent,
pubmed-meshheading:20713550-Cell Line,
pubmed-meshheading:20713550-Dual Specificity Phosphatase 1,
pubmed-meshheading:20713550-Dual-Specificity Phosphatases,
pubmed-meshheading:20713550-Enzyme Activation,
pubmed-meshheading:20713550-Humans,
pubmed-meshheading:20713550-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:20713550-Keratinocytes,
pubmed-meshheading:20713550-Mitogen-Activated Protein Kinase Phosphatases,
pubmed-meshheading:20713550-Signal Transduction,
pubmed-meshheading:20713550-Thapsigargin,
pubmed-meshheading:20713550-Up-Regulation,
pubmed-meshheading:20713550-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2010
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| pubmed:articleTitle |
Thapsigargin induces expression of activating transcription factor 3 in human keratinocytes involving Ca2+ ions and c-Jun N-terminal protein kinase.
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| pubmed:affiliation |
Department of Medical Biochemistry and Molecular Biology, Building 44, University of Saarland Medical Center, D-66421 Homburg, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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