Differences in electron transport potential, antioxidant defenses, and oxidant generation in young and senescent fetal lung fibroblasts (WI-38)

The activities and mRNA abundances of enzymes that regulate the rate of ele ctron flow through the electron transport chain (ETC), including NADH dehyd rogenase, succinate dehydrogenase, and cytochrome c oxidase, were examined in young and senescent fetal lung fibroblasts (WI-38). We also determined t he activities and mRNA abundances of antioxidant defenses including superox ide dismutase, catalase, and glutathione peroxidase. WE confirmed our previ ous report of a senescence-related increase in the abundance of ND4, a mito chondrially encoded subunit of NADH dehydrogenase. The activities of cytoch rome c oxidase and NADH dehydrogenase were also elevated in senescent cultu res. No differences were observed in the mRNA abundances of COX-1, a mitoch ondrially encoded subunit of cytochrome c oxidase or of nuclearly encoded s ubunits of various electron transport components (SD, COX-4, and ND 51). Lu cigenin-detected chemiluminescence and H2O2 generation were both elevated i n senescent cells. Catalase activity was also elevated in senescent fibrobl asts. However, no differences in catalase mRNA abundance were observed. A s mall decrease in GSH peroxidase (GPx) mRNA abundance was observed in senesc ent cells. No other changes in the activities or mRNA abundances of any of the antioxidant defenses were observed in early and late passage cultures. The relationships between oxidant generation, mitochondrial enzyme activiti es, and antioxidant defense observed during proliferative senescence are di ssimilar to those detected between fetal and postnatal fibroblasts as well as those found between fibroblast lines obtained from young and old individ uals. The relevance of the differences between these models is discussed. ( C) 1999 Wiley-Liss, Inc.