RESUMO
Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances.
Assuntos
Envelhecimento/fisiologia , Morte Celular/fisiologia , Dano ao DNA/fisiologia , Radicais Livres , Humanos , Oxirredução , Oxigênio/metabolismo , Poli(ADP-Ribose) Polimerases/fisiologiaRESUMO
The type of DNA damage and the role of poly (ADP-ribosyl) polymerase (ADPRP) and sulphated glyprotein 2 (SGP-2) in programmed cell death (apoptosis) was investigated in the following model systems: i) rat thymocytes treated with dexamethasone (DEX) eitherin vitro orin vivo; ii) human perypheral blood mononuclear cells (hPBMCs) exposed to oxygen free radicals (OR); iii) K562 cell line killed by hPBCs during spontaneous (NK) or interleukin-2 (IL-2)-induced (LAK) cytotoxic activity. The results suggest that ADPRP and SGP-2 are involved in the apoptotic process, but their role probably differs according to the type of cell and the inducing damage/stimulus. Moreover, no simple correlation appears to exist between the extent of DNA damage and cell survival or cell death.