Over-expression of biomarkers of environmental stress in renal epithelial cells resulting from proapoptotic activity of adriamycin: an immunohistochemical assessment
Keywords:
biomarkers of environmental stress, HSP70, p-53, Kidney, Apoptosis, ImmunohistochemistryAbstract
Introduction: In previous studies authors examined renal cells in rats after adriamycin administration and showed over-expression of proapoptotic effector caspase 3 and also histological changes typical for apoptosis.The mechanisms of adriamycin cytotoxic action involve DNA damage, action of free radicals formed in the process of degradation of this antibiotic, and interactions of both mechanisms.
The aim of the current study was to investigate the early answer of renal cells on proapoptotic action of adriamycin. Using the same model of renal epithelial cells from rats treated with adriamycin author determined the expression of proteins (HSP70, p-53) which are known as a biomarkers of cellular stress, using the immunohisto-chemical three-step method.
Results and discussion: The results showed that examined in this experimental study cells in response to DNA damage, increased synthesis of p-53 protein and in response to oxidative stress, started overproduction of heat shock protein 70 as a repairing factor. The areas of immunolocalization of these proteins were quantified using an image analysis program. Overproduction of HSP70 is extremely favorable for cells exposed to stress, however it blocks the repair action of p-53.
Conclusion: It is also likely that HSP70 inhibitors administered with adriamycin might result in more effective anti-neoplastic therapy for this drug.
References
1. Pedrycz A, Boratyński Z, Olesiński I, Dudzińska M. Immunohistochemical assessment of renal tubular epithelial cell death after anthracyclines therapy. Bull Vet Inst Pulawy. 2009; 53: 719-724.
2. Pedrycz A, Boratyński Z, Drelich G. Apoptotic index and histological assessment of renal tubular epithelial cells during anthracycline-induced apoptosis. Influence of time. Bull Vet Inst Pulawy. 2010; 54: 55-58.
3. Demidenko ZN, Vivo C, Halicka HD, Li CJ, Bhalla K, Broude EV, Blagosklonny MV. Pharmacological induction of HSP 70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor-and cycle-arrest-mediated cytoprotection. Cell Death Differ 2006; 13: 1434-1441.
4. Drzewoski J, Robak T. Clinical pharmacology of anticancer drugs, Warsaw: Nauka, 1991.
5. Hsu YL, Kuo PL, Tzeng WS, Lin CC. Chalcone inhibits the proliferation of human breast cancer cell by blocking
cell cycle progression and inducing apoptosis. Food Chem Toxicol. 2006; 44: 704-13.
6. Kaeser MD, Iggo RD. Chromatin immunoprecipitation analysis fails to support the latency model for regulation of p53 DNA binding activity in vivo. Proc Natl Acad Sci USA. 2002; 99: 95-100.
7. Smith O. Cancer. Nota bene: The killer instinct of a p-53 target. Science. 2000; 290: 67.
8. Chmielewski M, Linke K, Zabel M, Szuber L. Apoptosis in the liver. Gastroent Pol 2003; 10: 453-462.
9. Yoo JL, Janz DM. Tissue-specific HSP70 levels and reproductive physiological responses in fishes inhabiting a metal-contaminated creek. Arch Environ Contam Toxicol 2003; 45: 110-20.
10. Schmitz I, Kirchhoff S, Krammer PH. Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol. 2000; 32: 1123-36.
11. Berthiaume JM, Oliveira PJ, Fariss MW, Wallace KB. Dietary vitamin e decreases Doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol 2005; 5: 257-268.
12. Żylicz M, King FW, Wawrzynow A. HSP 70 interactions with the p 53 tumor supressor protein. EMBO J 2001; 20: 4634-4638.
