Affiliations: Department of Medical Chemistry and Biochemistry, 2nd
Medical Faculty, Charles University, Prague, Czech Republic | Institute of Microbiology, Czech Academy of Sciences,
Prague, Czech Republic
Note: [] Address for correspondence: Prof. Jiří Wilhelm,
PhD., Department of Medical Chemistry and Biochemistry, 2nd Medical Faculty,
Charles University, Plzeňská 221, 150 00 Praha 5, Czech Republic.
Tel.: +420 257 296 309; Fax: +420 257 210 995; E-mail:
[email protected]
Abstract: Free radicals are considered the most important cause of cellular
ageing. We have investigated ageing process in the yeast Saccharomyces
cerevisiae. We have compared the wild type strain with the mutant cells with
constitutively active Ras oncogen, which generates increased amounts of free
radicals. Increased generation of oxygen-derived free radicals resulted in the
Ras mutant cells accumulation of lipofuscin-like pigments during ageing. Ageing
wild type cells did not accumulate lipofuscin-like pigments. This is quite
unique feature among known biological models. It may be caused by increased
concentration of alpha tocopherol (the most prominent lipophilic antioxidant)
in the wild type cells. In contrast, the Ras mutant cells contained decreased
levels of alpha tocopherol even in the young cells. This observation indicates
that the increased free radical generation can overwhelm the endogenous
antioxidant system. We have documented the involvement of nitrogen-derived free
radicals in the yeast metabolism. Protein nitrotyrosine, a marker of the
reactive nitrogen species, has significantly increased in the senescent Ras
mutant cells. The wild type cells contained basic level of nitrotyrosine
corresponding to its concentration found in non-activated mammalian
macrophages.
