Title | Hydroxyurea and thalidomide as regulators of caspase-3 activity on rat spleen and intestinal epithélia | |
Author | H. Frangou-Massourides and A. KotsisDept Gen. Biology, Medical School, Aristotle University, Thessaloniki, Greece | |
Citation | Frangou-Massourides, H. and Kotsis, A.: Hydroxyurea and thalidomide as regulators of caspase-3 activity on rat spleen and intestinal epithélia, Epitheorese Klin. Farmakol. Farmakokinet. 18(1): 109-111 (2004) | |
Publication Date | Accepted for publication: 2004 | |
Full Text Language | English | |
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Keywords | Hydroxyurea, Thalidomide, Casspase-3 Activity, Intestinal Epithelia | |
Other Terms | review article | |
Summary | Apoptosis, an active form of cellular suicide with many well-defined morphological and biochemical features, is mediated by a family of proteases called caspases. Caspase-3 works as an effector, cleaving various death substrates that ultimately cause morphological and biochemical changes seen in apoptotic cells. Thalidomide besides its teratogenic and anti-angiogenic effects, influences Bcl2 expression, a gene involved in apoptosis. Hydroxyurea acts as a chemotherapeutic agent useful in neoplastic diseases. In the present study we investigated Ihe role of thalidomide and hydroxyurea on caspase-3 activity in subcellular fractions of rat spleen and intestinal epithelia. Caspase-3 activity was determined on subcellular fractions of the above tissues, obtained according to the method of Nordlie and Lardy. Caspase-3 activity was estimated by a colorimetric assay, based on the hydrolysis of the peptide substrate acetyl-Asp-Glu-Val-Asp p-nitroanline (pNA) moiety. Caspase-3 activity was calculated in pmoi pNA released per min per ml. Our results demonstrate that hydroxyurea and thalidomide may induce programmed cell death probably by down regulation of caspase-3 activity, on rat spleen, and by up-regulation, on rat intestinal epithelia. Based on our findings, the most likely mechanism that can account for the biological effects of thalidomide and hydroxyurea, in rat spleen and intestinal epithelia, involves the induction of caspase-dependent apoptotic cell death. | |
References | 1. Marriott J.B., et al.: A novel subclass of thalidomide analogue with anti-sotid tumor activity in which caspase- dependent apoptosis is associated with altered expression of bcl-2 family proteins. Cancer Res. 63. 593-599 (2003)2. Katzung B.C.: Basic and Clinical Pharmacology. Pp. 914-917, 6fd ed, Appleton & Lange, California, 1995
3. Schwab M.: Encyclopedic Reference of Cancer. Pp. 73- 77, Springer, Berlin, 2001 4. Nickolson D.W., Thornberry A.: Caspases: killer proteases. Trends Biochem. Sci. 22: 299-306 (1997) 5. Schwab M.: Encyclopedic Reference of Cancer. P.p 167- 169, Springer, Berlin, 2001 6. Nordlie R.C., Lardy H.A.: Subcellular distribution of rat liver PPiase activity. Biochem. Biophys. Acta 50. 189-191 (1961) 7. Cohen G.M.: Caspases: the executioners of apoptosis. Biochem. J. 326:1-16 (1997) |
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Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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