| Title | Lysosomal enzymes mediated apoptosis in rat hypertrophied kidney after treatment with hydroxyurea and thalidomide | |
| Authors | Helen Frangou and Nikol Massouridou
Dept. of Gen. Biology Medical School, Aristotle University of Thessaloniki, Greece |
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| Citation | Frangou, H., Massouridou, N.: Lysosomal enzymes mediated apoptosis in rat hypertrophied kidney after treatment with hydroxyurea and thalidomide, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 159-161 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Hydroxyurea, thalidomide, lysosomes mediated apoptosis, hypertrophied kidney, hyperplasia. | |
| Other Terms | review article | |
| Summary | Apoptotic death is implicated in sculpting (e.g, loss of webs between digits), deleting unwanted formed structures (e.g, involution of the mesonephros), and adjusting cell numbers (e.g, deleting excess precursors in the metanephric kidney). We have undertaken this study for better understanding the cellular mechanisms involved in Hydroxyurea (HU) and Thalidomide (Thal) in nephrotoxicity, by determining the lysosomal proteolytic activity of normal and hypertrophied rat kidneys, since these drugs have been characterized as cytotoxic and induce apoptosis. We used male rats (Wistar) of 230-260 g of weight. Half of them have undergone unilateral nephrectomy according to the method of Waynforth. Nephrectomized and no nephrectomized rats were divided into four groups. Groups A (controls) were injected intra- muscularly with NaCl 9%o. Groups B were injected with HU 4.56 mglk.b. weight. Groups C were injected with Thal 15.45 mglk.b. weight, and groups D with HU and Thal in combination, as above. Animals were sacrificed at 24, 48 and 72 hours after injections. The kidneys were removed and homogenized with a Potter Elvehjem homogenizer and lysosomal fraction was obtained according to the method of Nordlie and Lardy. Proteolytic activity was determined, by the Goodwin’s method. According to our results we found enhanced lysosomal proteolytic activity in normal and hypertrophied kidneys after 48 and 72 hrs treatment with HU. We observed the same results after Thal administration. It is concluded that enhanced proteolytic activity mediated by lysosomal enzymes may con- tribute to apoptosis or lead to inappropriate cell death and decreased cell numbers in cytotoxic cases after HU and Thal treatment. | |
| References | 1. Guicciardi M., Denssing J., Miyoshi H., Bronk S., Svingen P.A., Peters C., Kaufmann S.H., Gores G.J.: Cathepsin B contributes to TNF-a-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J. Clin. Invest.106: 1127-1137 (2000)
2. Kagedal K., Johansson U., Ollinger K.: The lysosomal pro- tease cathepsin D mediates apoptosis by oxidative stress. Faseb. Jour. 15: 1592-1594 (2001) 3. Stoka V., Turk B., Schendel J., Kim T., Cirman T., Snipas S., Ellerby L., Bredesen D., Hudson F., Abrahamson M., Bromme D., Krajewski S., Reed J., Yin X., Turk V., Salvesen G.: Lysosomal Pathways to Apoptosis: Cleavage of BID not pro-caspases is the most likely route. J. Biol. Chem. 276: 3149-3157 (2001) 4. Frangou-Massourides H.: The role of lysosomal proteases in apoptosis induced by hydroxyurea and thalidomide in rat lymph nodes. Proceedings of the 56th Meeting of HellenicSociety of Biochemistry & Molecular Biology, Larissa 2004, Vol 51, http://www.adobe.com/acrobat 5. Park M., Helip-Wooley A., Thoene J.: Lysosomal cystine storage augments apoptosis in cultured human fibroblasts and renal ubular epithelial cells. J. Am. Soc. Nephrol. 13: 2878- 2887 (2002) 6. Frangou-Massourides H.: Thalidomide and Hydroxyurea: their anti-apoptotic effect on regeneration rat liver. Scientific Annals of the Faculty of Medicine, Aristotle University of Thessaloniki 31(2): 73-79 (2004) 7. Frangou-Massourides H., Kotsis A.: Hydroxyurea and Thalidomide – mediated regulation of caspase-3 activity on rat spleen and intestinal apithelia. Scientific Annals of the Faculty of Medicine, Aristotle University of Thessaloniki 31(2): 9-11 (2004) 8. Waynforth H.B.: Experimental and Surgical Technique in the Rat. Pp. 159-160, Academic Press, London, 1980 9. Nordlie R.C., Lardy H.A.: Subcellular distribution of rat liver PPiase activity. Biochim. Biophys. Acta 50: 189-191 (1961) 10. Goodwin J.F.: Determination of Amino Acid Nitrogen and Urine. In: (Henry R.J., Cannon D.C., Winkelman J.W., eds) Clinical Chemistry, Principles and Technics. P. 571, Harper and Row Publishers. 1974 11. Welham S.J., Wade A., Woolf A.S.: Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int. 61: 1231-1242 (2002) 12. Lassmann G., Thelander L., Graslund A.: EPR stopped- flow studies of the reaction of the tyrosyl radical of protein R2 from ribonucleotide reductase with hydroxyurea. Biochem. Biophys. Res. Commun. 188: 879-887 (1992) 13. Yen A., Varvayanis S.: RB tumor suppressor gene expression responds to DNA synthesis inhibitors. In Vitro Cell. Dev. Biol. 28a: 669-672 (1992) 14. Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y., Horvitz H.R.: Translocation of C. elegans CED- 4 to nuclear membranes during programmed cell death. Science 287: 1485-1489 (2000) 15. Harousseau J.L., Shaughnessy J., Richardson P.: Multiple myeloma. Hematology 1: 237-56 (2004) 16. Barille-Nion S., Barlogie B., Bstaille R., Bergsagel P.L., Epstein J., Fenton R.G., Jacobson J., Kuehl W.M., Shaughnessy J., Tricot G.: Advances in biology and therapy of multiple myeloma. Hematology (Am Soc Hematol Educ Program): 248- 278 (2003) 17. Yeo E.J., Hwang Y.C., Kang C.-M., Kim I.H., Kim D.I., Parka J.S., Choy H.E., Park S.C.: Senescence-like changes induced by hydroxyurea in human diploid fibroblasts. Exp. Gerontol. 35: 553-571 (2000) |
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Online ISSN 1011-6575
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