[Oxidative stress, age-dependent [correction of age-related] cell damage and antioxidative mechanisms].
Cellular oxidative stress is due to the production of reactive oxygen species (ROS), on the one hand, and weaknesses of the antioxidative defence, on the other. This is particularly true for cells with an active metabolism such as neurons and muscle cells, but it is also relevant for all other cell types. Hydrogen peroxide is an important member of ROS and is generated predominantly by mitochondria. In combination with reduced trace metals such as iron or copper, hydrogen peroxide is transformed into the highly reactive hydroxyl radical which causes damage to virtually all macromolecules. Oxidation of nucleic acids results in mutations while protein denaturation leads to enzyme defects and impairment of the cytoskeleton. Lipid peroxidation in cell membranes is strongly involved in the perturbation of ion homeostasis. Because this cell damage ultimatively causes cell death, oxidative stress initiates several diseases. Mitochondria play a major role in this context because they are the main source of endogenous oxidative stress and additionally function as an inducer of programmed cell death (apoptosis). Several strategies of antioxidative defence exist: While transition metals can be inactivated by chelating proteins (e.g., ferritin), ROS can be reduced enzymatically (e.g., by the glutathione peroxidase) or non-enzymatically by antioxidants (e.g., by vitamin E, vitamin C and glutathione). Stress proteins are implicated in the repair and transport of denatured proteins as well as in the inhibition of apoptosis.
Gosslau
Alexander
A
Institut für Zellbiologie Biochemie und Biotechnologie Universität Bremen Postfach 330440 28334 Bremen, Germany.
Rensing
Ludger
L
D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000502:physiology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*
D000975:Antioxidants; D005979:Glutathione Peroxidase