老化与抗氧化能力及其相关分子检测.ppt

老化與抗氧化能力及其相關分子檢測 Dr.曾婉芳 Oxidative stress Oxidative Stress Reactive oxygen species (ROS) ROS and oxidative stress Antioxidant system Oxidative damage Oxidative stress and apoptosis Oxidative stress and aging Oxidative stress and cancer ROS as signaling molecules Reactive oxygen species (ROS) ROS OH. (hyroxyl radical) O2-. (superoxide radical) H2O2 (hydrogen peroxide) NO. (nitric oxide) Oxidative stress Oxidative damage Toxic effects of ROS Protein oxidation Lipid peroxidation Nucleic acids damage Double-strand DNA breaks Single-strand DNA breaks Change DNA bases 8-oxoguanine Thymine glycol Lipid peroxidation Measure the malondialdehyde formed Lipid peroxidation is a chain reaction. Each fatty acyl moiety that undergoes peroxidaion generate a radical that can initiate another peroxidation reaction. Intracellular sources of free radicals Mitochondrial electron transport system Superoxide radical and semiquinone radical Microsomal (ER) electron transport system Superoxide radical and H2O2 Arachidonic acid metabolism Reactions within peroxisome Superoxide radical and H2O2 Intracellular sources of free radicals In cytosol Xanthine oxidase oxidizes xanthine and generates H2O2 Amino acid oxidases generates H2O2 as their ordinary products H2O2 and O2-. may diffuse from their subcellular sites of production and affect the whole cell H2O2 can cross biological membranes NO. synthesis Reactive nitrogen species (RSN) Inactivation of respiratory chain complexes; inhibition of protein and DNA synthesis RNS are reduced or inactivated through the generation of a disulfur bond between two glutathione molecules to form oxidized glutathione Dietary oxidants Generation of ROS ROS are reduced or inactivated through the generation of a disulfur bond between two glutathione molecules to form oxidized glutathione Xenobiotics Man-made compounds with chemical structures foreign to a given organism Induce cancer Glutathione is involved in the conjugation of epoxides to less toxic compounds