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Iron deprivation induces apoptosis independently of p53 in human and murine tumour cells
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SYSNO ASEP 0105357 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title Iron deprivation induces apoptosis independently of p53 in human and murine tumour cells Title Nedostatek železa vyvolává apoptózu nezávisle na p53 v lidských a myších nádorových buňkách Author(s) Truksa, Jaroslav (UMG-J)
Kovář, Jan (UMG-J)
Valenta, Tomáš (UMG-J) ORCID
Ehrlichová, Marie (UMG-J)
Polák, J. (CZ)
Naumann, P. W. (US)Source Title Cell Proliferation - ISSN 0960-7722
Roč. 36, č. 4 (2003), s. 199-213Number of pages 15 s. Language eng - English Country GB - United Kingdom Keywords iron deprivation ; p53 ; apoptosis induction Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA301/01/0041 GA ČR - Czech Science Foundation (CSF) Annotation Iron deprivation induces apoptosis in some sensitive cultured tumour cells, while other cells are resistant. In order to elucidate the mechanisms involved in apoptosis induction by iron deprivation, we studied the expression of p53 and the expression of selected p53-regulated genes. To discriminate between changes coupled only with iron deprivation and changes involved in apoptosis induction by iron deprivation, we compared the expression of the genes in sensitive (human Raji, mouse 38C13) versus resistant (human HeLa, mouse EL4) cells under iron deprivation. Iron deprivation was achieved by incubation in a defined iron-free medium. The level of p53 mRNA decreased significantly under iron deprivation in sensitive cells, but it did not change in resistant cells. On the contrary, the level of the p53 protein under iron deprivation was slightly increased in sensitive cells while it was not changed in resistant cells. The activity of p53 was assessed by the expression of selected p53-regulated targets, i.e. p21WAF1/CIP1 gene, mdm2, bcl-2 and bax. We did not detect any relevant change in mRNA levels as well as in protein levels of these genes under iron deprivation with the exception of p21WAF1/CIP1. We detected a significant increase in the level of p21 mRNA in both (sensitive and resistant) mouse cell lines tested, however, we did not find any change in both (sensitive and resistant) human cell lines. Moreover, the p21WAF1/CIP1 protein was accumulated in mouse-sensitive 38C13 cells under iron deprivation while all other cell lines tested, including human-sensitive cell line Raji, did not show any accumulation of p21WAF1/CIP1 protein. It seems that the p21WAF1/CIP1 mRNA, as well as protein accumulation, is not specifically coupled with apoptosis induction by iron deprivation and that it is rather cell-line specific. Taken together, we suggest that iron deprivation induces apoptosis at least in some cell types independently of the p53 pathway Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2005
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