| Activation of intrinsic apoptotic pathway by Re-188 irradiation and paclitaxel in coronary artery smooth muscle cells. | |
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MedLine Citation:
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PMID: 17380098 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: Intravascular brachytherapy efficiently reduces vascular smooth muscle cell (SMC) proliferation, interstitial matrix production, vascular remodeling and restenosis rate after revascularization injury of coronary arteries. In this study we examined the molecular mechanisms of the cytotoxic effect of Re-188-mediated beta-irradiation on a SMC culture model compared to that of paclitaxel. METHODS: SMC were irradiated with 1, 3, 10 and 30 Gy with Re-188 or treated with 1, 5, 10 microg/mL paclitaxel. After 24, 48 and 72 h, cell death, apoptosis pathways and cell cycle were examined. RESULTS: Irradiation and paclitaxel induced cell cycle arrest in G1. Dose-dependent cell death ranged from 40% at 1 Gy to 80% at 30 Gy irradiation, and induced in 45% of SMC treated with paclitaxel. Irradiation induced increasing rates of necrotic cell death up to 40% at 30 Gy. Activation of caspase-3 was detected, and poly(ADP-ribose)polymerase (PARP), the prototype substrate of caspases, was cleaved upon beta-irradiation. In addition, beta-irradiation-mediated apoptosis activated caspase-9, indicating that mitochondria were involved. Further-more, Bax was upregulated. However, upregulation of death-inducing ligands (DIL) or receptors (DIL-R) was not involved in beta-irradiation-induced apoptosis in SMC. Similar to beta-irradiation, the intrinsic mitochondrial apoptosis pathway was activated by paclitaxel. CONCLUSION: These findings demonstrate that beta-irradiation and paclitaxel induced apoptosis and activated apoptosis signaling pathways in SMC at several levels by triggering intrinsic mitochondrial but not external death receptor mediated pathways. |
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Authors:
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C Friesen; A Lubatschofski; G Glatting; K M Debatin; S N Reske |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-25 |
Journal Detail:
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Title: The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of Radiopharmaceutical Chemistry and Biology Volume: 52 ISSN: 1824-4785 ISO Abbreviation: - Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-06-19 Completed Date: 2008-09-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101213861 Medline TA: Q J Nucl Med Mol Imaging Country: Italy |
Other Details:
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Languages: eng Pagination: 289-95 Citation Subset: IM |
Affiliation:
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Department of Nuclear Medicine, University of Ulm, Ulm, Germany. claudia.friesen@uni-ulm.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* Cell Death Cell Proliferation Coronary Vessels / drug effects*, pathology*, radiation effects* Dose-Response Relationship, Drug Gene Expression Regulation* Ligands Mitochondria / metabolism Myocytes, Smooth Muscle / drug effects*, pathology*, radiation effects* Necrosis Paclitaxel / pharmacology Radioisotopes / chemistry* Radiometry Rhenium / chemistry* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Radioisotopes; 33069-62-4/Paclitaxel; 7440-15-5/Rhenium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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