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

Abstract

The activities and mRNA abundances of enzymes that regulate the rate of electron flow through the electron transport chain (ETC), including NADH dehydrogenase, succinate dehydrogenase, and cytochrome c oxidase, were examined in young and senescent fetal lung fibroblasts (WI-38). We also determined the activities and mRNA abundances of antioxidant defenses including superoxide dismutase, catalase, and glutathione peroxidase. We confirmed our previous report of a senescence-related increase in the abundance of ND4, a mitochondrially encoded subunit of NADH dehydrogenase. The activities of cytochrome c oxidase and NADH dehydrogenase were also elevated in senescent cultures. No differences were observed in the mRNA abundances of COX-1, a mitochondrially encoded subunit of cytochrome c oxidase or of nuclearly encoded subunits of various electron transport components (SD, COX-4, and ND 51). Lucigenin-detected chemiluminescence and H2O2 generation were both elevated in senescent cells. Catalase activity was also elevated in senescent fibroblasts. However, no differences in catalase mRNA abundance were observed. A small decrease in GSH peroxidase (GPx) mRNA abundance was observed in senescent 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 activities, and antioxidant defense observed during proliferative senescence are dissimilar to those detected between fetal and postnatal fibroblasts as well as those found between fibroblast lines obtained from young and old individuals. The relevance of the differences between these models is discussed.

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

“…This finding is consistent with previous studies showing that NADH dehydrogenase expression increases with advancing age in the muscle of rats (Chang et al 2007) and in lung fibroblasts of humans (Allen et al 1999). ATP synthase expression also increased with advancing age in the trophocytes and fat cells of workers.…”

Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue

“…Therefore, ROS have been implicated to play a causal role in tissue degeneration and -if deviant in composition and concentration -also in cancer and aging. Increased ROS concentration occurs in senescent fibroblast in vitro and in vivo (Scharffetter-Kochanek et al, 1997;Allen et al, 1999;Hutter et al, 2002;Shin et al, 2005). Fibroblasts constitute the principal component of the connective tissue.…”

Proteasome modulates mitochondrial function during cellular senescence

“…Although a small decrease to an insignificant change has been observed in mRNA abundances of gluthathione peroxidase and superoxide dismutases SOD1, SOD2 respectively, their activities were stable during the replicative senescence of WI-38 fibroblasts [53]. However, catalase activity has been reported threefold higher in senescent cells compared to early passage cells which is consistent with the hypothesis that senescence-associated increase in oxidant production stimulate cell to increase their catalase activity.…”

“…However, catalase activity has been reported threefold higher in senescent cells compared to early passage cells which is consistent with the hypothesis that senescence-associated increase in oxidant production stimulate cell to increase their catalase activity. Young cultures increase their GSH concentration in response to oxygen tension however only at ambient oxygen tensions that exceed 35% oxygen this capacity decrease in senescent cells [53]. Consequently, proteasome dysfunction appears as one consistent mechanism linking oxidative stress during replicative senescence of human cells.…”

“…Previous studies have shown an inconsistent relation between rate of oxidant generation and pattern of changes in antioxidants defenses in cell cultures established from young and old tissues or during replicative senescence [51], [52] and [53]. Although a small decrease to an insignificant change has been observed in mRNA abundances of gluthathione peroxidase and superoxide dismutases SOD1, SOD2 respectively, their activities were stable during the replicative senescence of WI-38 fibroblasts [53].…”