Lovastatin-induced apoptosis in thyroid cells: involvement of cytochrome c and lamin B
| Autor: | Gf Fenzi, T. Di Matola, Cristina Luongo, Maurizio Bifulco, Guido Rossi, Mario Vitale, F. D’Ascoli |
|---|---|
| Přispěvatelé: | DI MATOLA, T, D'Ascoli, F, Luongo, C, Bifulco, M, Fenzi, Gf, Rossi, Guido, Vitale, M., Rossi, G, Fenzi, Gianfranco |
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Blotting Western Caspase 2 Thyroid Gland bcl-X Protein Apoptosis Cytochrome c Group Caspase 3 Cytosol Endocrinology Bcl-2-associated X protein Western blot Proto-Oncogene Proteins Internal medicine medicine Humans Lovastatin Cells Cultured bcl-2-Associated X Protein Caspase 6 Lamin Type B biology medicine.diagnostic_test Cytochrome c Antibodies Monoclonal Nuclear Proteins General Medicine Genes p53 Lamins Genes bcl-2 Up-Regulation Enzyme Activation Proto-Oncogene Proteins c-bcl-2 Caspases biology.protein Lamin medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje.0.1450645 |
| Popis: | OBJECTIVE: The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, lovastatin, induces apoptosis in the thyroid cell line TAD-2 and in proliferating normal human thyroid cells in culture, through a p53-independent mechanism involving caspase-3-like proteases. The combination of lovastatin with other anti-neoplastic drugs potentiates chemotherapy of tumors. This drug has been suggested for the chemotherapy of tumors and is potentially useful in the treatment of thyroid proliferative diseases. Based on this premise, we analyzed in more detail the role of some molecular effectors and the role of the caspase family proteases in the lovastatin-induced apoptotic pathway in TAD-2 cells. METHODS: TAD-2 cells were treated with lovastatin to induce apoptosis, and expression of p53, Bc1-2, Bcl-XL and Bax was analyzed by Western blot. Caspase activation was evaluated by the assay of enzymatic activity with chromogenic peptides and Western blot. Nuclear, cytosolic and mitochondrial fractions were prepared by differential centrifugation and the presence of cytochrome c and lamin B was evaluated by Western blot. RESULTS: p53, Bc1-2, Bcl-XL and Bax protein expression were unchanged during apoptosis. Cytochrome c was released from mitochondria into the cytosol, a pivotal event in the activation of caspase-3. Caspase-3 and -6 but not caspase-2 were activated, and proteolysis of PARP and lamin B, a caspase-6 substrate located in the inner nuclear membrane, was demonstrated by Western blot. The nuclear localization of lamin B was also inhibited by lovastatin. CONCLUSIONS: These data demonstrate that, in TAD-2 thyroid cells, lovastatin induces lamin B proteolysis and inhibits its nuclear localization and induces cytochrome c release from mitochondria into the cytosol. |
| Databáze: | OpenAIRE |
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