Expression of hydrogen peroxide and glutathione metabolizing enzymes in human skin fibroblasts derived from donors of different ages

Keogh, Bart P.; Allen, Robert G.; Pignolo, Robert J.; Horton, Joseph; Tresini, Maria; Cristofalo, Vincent J.

doi:10.1002/(sici)1097-4652(199606)167:3<512::aid-jcp15>3.0.co;2-5

Cited by 45 publications

(14 citation statements)

References 69 publications

(60 reference statements)

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“…The reducing potential of the cell in terms of the additional bioconversion of GSSG to GSH may protect the cells from free-radical-mediated damage and account for the increase in the cellular growth as has been observed in old human fibroblasts treated with antioxidants (9). This hypothesis is consistent with previous studies that indicate that cellular aging is associated with a general deficiency of glutathione (1,22). Table 1-1 shows that WSP and HC treatments resulted in a significant increase in GSSG concentration in PDL 20→50 cells.…”

Section: Discussionsupporting

confidence: 92%

Effects of Radical Scavenger Protein from Broad Beans on Glutathione Status in Human Lung Fibroblasts

Okada

Okada²

2007

Environ. Health Prev. Med.

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Objective: Human diploid cells are more susceptible to oxidative stress at late passage than at early passage, presumably because of the decrease in cellular-reduced glutathione (GSH) concentration. Water-soluble protein (WSP) from broad beans scavenges free radicals. The effects of WSP on the glutathione system were examined in PDL 20 (early passage) and PDL 50 (late passage) human lung fibroblasts (TIG-1).Methods: To determine cytosolic glutathione peroxidase (GSH-Px) activities, glutathione reductase (GR) activities, oxidized glutathione (GSSG) concentrations, and GSSG/reduced glutathione (GSH) ratios, WSP and hydrocortisone (HC) treatments of TIG-1 cells (PDL 20→50 and PDL 50→75) were performed for 40 days. We also investigated the GSSG concentrations and GR activities in PDL 20 cells that were continuously treated with WSP until PDL 39 and 55.Results: GSSG concentrations decreased in WSP-and HC-treated PDL 50→75 cells. The GSSG/ GSH ratios in PDL 50→75 cells became low after the treatments. Increases in GR activities were observed in treated PDL 50→75 cells. The decline in the GSSG concentration of PDL 50→75 cells correlated with the increase in GR activity. The GSSG levels in control cells were higher following cellular age, whereas the levels in treated cells were lower than those in the control. The studies on cellular age-related changes indicated that greater increases in GR activity were found in treated cells than in the control.Conclusion: These results indicated that WSP influences the GSSG concentration that is associated with cellular aging, but the mechanism of GSSG reduction by WSP remains unknown. The enhancement of glutathione status following WSP treatment may be related to the delay in the cellular aging.

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Section: Discussionsupporting

confidence: 92%

Effects of Radical Scavenger Protein from Broad Beans on Glutathione Status in Human Lung Fibroblasts

Okada

Okada²

2007

Environ. Health Prev. Med.

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“…These include superoxide dismutases (SOD) that remove superoxide radicals (O 2 .- ) and produce hydrogen peroxide (H 2 O 2 ; Allen 1998), and catalase and peroxidases that remove H 2 O 2 (Keogh et al 1996). The family of seleno-proteins referred to as GSH peroxidases (GPx) remove both H 2 O 2 (Modrick et al 2009) and lipid peroxides (Ran et al 2006; Arsova-Sarafinovska et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Effects of oxygen, growth state, and senescence on the antioxidant responses of WI-38 fibroblasts

Balin

Reimer

Reenstra

et al. 2010

AGE

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Mitotically active, growth-arrested cells and proliferatively senescent cultures of human fetal lung fibroblasts (WI-38) were exposed to six different oxygen tensions for various lengths of time and then analyzed to determine the responses of their antioxidant defense system. Glutathione (GSH) concentration increased as a function of ambient oxygen tension in early passage cultures; the effect was larger in exponentially growing cultures than in those in a state of contact-inhibited growth arrest, but was absent in senescent cells. Conversely, the activity of glutathione disulfide reductase was greater in growth-arrested cultures than in mitotically active cells irrespective of oxygen tension. Glucose-6-phosphate dehydrogenase was lowest in log-phase cells exposed to different oxygen tensions for 24 h and in senescent cells. Both hypoxia and hyperoxia depressed selenium-dependent glutathione peroxidase activity in early passage cultures, while the activity of the enzyme progressively declined with increasing oxygen in senescent cells. The GSH S-transferase activity was unresponsive to changes in ambient oxygen tension in either young or senescent cultures. Manganese-containing superoxide dismutase (MnSOD) activity was unaffected by oxygen tension, but was elevated in young confluent cultures as compared with cultures in log-phase growth. MnSOD activity was significantly higher in senescent cultures than in early passage cultures and was also responsive to increased oxygen tension in senescent cultures. Copper–zinc-containing superoxide dismutases activity was not affected by oxygen tension or the passage of time, but it declined in senescent cultures.

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“…20 and 21). The activities of enzymic antioxidant defenses tend to be lower in fetal cells than in cells derived from postnatal tissues (22)(23)(24); however, the GSH concentration is frequently greater in fetal cells than in cells from adults (20,24). Whether these observations reflect differences in the steadystate level of ROS in fetal and postnatal cells is not presently known (20,21).…”

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confidence: 99%

“…Additionally, we determined the mRNA abundance of succinate dehydrogenase (SD), which is encoded entirely by the nuclear genome (33,34) for a comparison with the nuclear encoded subunits of the mosaic enzymes examined. We have determined previously that the skin fibroblast model, used in this study, maintains the development and age-dependent differences in antioxidant defenses known to exist in numerous organisms and tissues in vivo (22)(23)(24).…”

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Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Allen

Keogh²,

Tresini

et al. 1997

Journal of Biological Chemistry

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We determined the activities of NADH dehydrogenase (ND), succinate dehydrogenase, and cytochrome c oxidase (COX) in 29 skin fibroblast lines established from donors ranging in age from 12 gestational weeks to 94 years. The results of this study demonstrate that all three of the enzyme activities examined are greater in adult-derived fibroblasts than in the fetal cell lines. The ratio of enzyme activities that control electron entry into and exit from the electron transport chain varied directly with lucigenin-detected chemiluminescence (an indicator of ⅐ O 2 ؊ generation) and inversely with H 2 O 2 generation. These results indicate a clear difference in the predominant oxidant species generated during fetal and adult stages of life. We also examined the mRNA abundances of different components of the electron transport chain complexes. We observed higher abundances of mitochondrial encoded mRNAs (COX 1 and ND 4) in cell lines established from adults than in fetal cells. No differences in the mRNA abundances of the nuclear encoded sequences (COX 4 and ND 51) were observed in fetal and postnatal-derived lines. Succinate dehydrogenase mRNA abundance was greater in cell lines established from postnatal donors than in fetal cell lines. No significant differences between cell lines established from young and old adults were detected in any of the parameters examined.Mitochondria are the primary site of aerobic energy production and are thus the major site of generation of reactive oxygen species (ROS), 1 such as oxygen-centered free radicals and peroxides, which are by-products of metabolism (1-4). Estimates of the rate of ROS generation can differ greatly; however, it has been demonstrated repeatedly that the relative rate of oxidant generation increases with age and that this increase correlates strongly with age-associated changes in the cellular redox state (5-8). For example, the rates of superoxide ( ⅐ O 2 Ϫ ) (8 -14) and H 2 O 2 generation (7, 10, 14 -17) increase in the cells of aging organisms, whereas the glutathione concentration declines progressively with advancing age (5,6,18,19). Differences in ROS metabolism also exist between cells obtained from early developmental stages and from postnatal tissues (for review, see Refs. 20 and 21). The activities of enzymic antioxidant defenses tend to be lower in fetal cells than in cells derived from postnatal tissues (22-24); however, the GSH concentration is frequently greater in fetal cells than in cells from adults (20,24). Whether these observations reflect differences in the steadystate level of ROS in fetal and postnatal cells is not presently known (20, 21).The rate of mitochondrial ROS generation in cells is largely dependent on the amounts of autoxidizable respiratory carriers and the redox state of electron carriers (1,3,25,26). All electron carriers located prior to one of low abundance will exhibit a greater propensity to be chemically reduced because of the slowing of electron flux (electron stacking; 1, 16, 25, 27). Thus, either age or development-a...

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Expression of hydrogen peroxide and glutathione metabolizing enzymes in human skin fibroblasts derived from donors of different ages

Cited by 45 publications

References 69 publications

Effects of Radical Scavenger Protein from Broad Beans on Glutathione Status in Human Lung Fibroblasts

Effects of Radical Scavenger Protein from Broad Beans on Glutathione Status in Human Lung Fibroblasts

Effects of oxygen, growth state, and senescence on the antioxidant responses of WI-38 fibroblasts

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

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