Role of Free Radicals in Senescence

Allen, Robert G.

doi:10.1007/978-3-662-38445-9_12

Cited by 3 publications

(5 citation statements)

References 46 publications

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“…As with MnSOD MRNA levels, these stimuli also induced MnSOD protein levels. , 1993;Beckman, 1994), neurotoxicity (Choi, 1988;Choi et al, 1988;Dawson et al, 1993;Lafon-Cazal et al, 1993), and aging (Allen, 1990;Bondy, 1992;Halliwell, 1992). For example, it has recently been demonstrated that mutations in Cu!…”

Section: Resultsmentioning

confidence: 99%

“…Given the importance of intracellular concentrations of 02 and NOã nd their potential for ONOO formation, we studied MnSOD, Cu/ZnSOD, and iNOS gene expression in primary cultures of rat neurons and glial cells. Furthermore, because various studies have implicated oxygen free radicals during aging (Allen, 1990;Bondy, 1992;Halliwell, 1992), we evaluated glia from 3-, 21-, and 95-day-old rats.…”

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confidence: 99%

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Regulation of the Manganese Superoxide Dismutase and Inducible Nitric Oxide Synthase Gene in Rat Neuronal and Glial Cells

Kifle

Monnier

Chesrown

et al. 1996

Journal of Neurochemistry

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Bidirectional communication occurs between neuroendocrine and immune systems through the action of various cytokines. Responses to various inflammatory mediators include increases in intracellular reactive oxygen species (ROS), notably, superoxide anion (02) and nitric oxide (N0). Neurotoxicity mediated by N0 may result from the reaction of N0 with 02, leading to formation of peroxynitrite (ONOO-). ROS are highly toxic, potentially contributing to extensive neuronal damage. We, therefore, evaluated the effects of a vari~ty of inflammatory mediators on the regulation of mRNA levels for manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS) in primary cultures of rat neuronal and glial cells. To determine age-dependent variation of mRNA expression, we used glial cells derived from newborn, 3-, 21-, and 95-day-old rat brains. lnterleukin-i /3, interferon-y (IFN-y), bacterial lipopolysaccharide (LPS), and tumor necrosis factor-a showed significant induction of MnSOD in both glial and neuronal cells. However, only LPS and IFN-y increased 1NOS mRNA. These data demonstrate that these two genes are similarly regulated in two cells of the nervous system, further suggesting that the oxidative state of a cell may dictate a neurotoxic or neuroprotective outcome. Key Words: Superoxide dismutase-Inducible nitric oxide synthase-mRNA-Gene regulation-Neurons-Glia-Rat.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Regulation of the Manganese Superoxide Dismutase and Inducible Nitric Oxide Synthase Gene in Rat Neuronal and Glial Cells

Kifle

Monnier

Chesrown

et al. 1996

Journal of Neurochemistry

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“…The antioxidant defense system as well as parameters that influence oxidant production are of particular interest because many of them are known to change during develop-ment (Allen, 1990(Allen, , 1998Allen and Balin, 1989;Allen et al, 1991;Allen and Sohal, 1986) and aging in vivo (Hegner, 1980;Ku et al, 1993;Matsuo, 1993;Nohl and Hegner, 1978;Sohal and Sohal, 1991;Sohal et al, 1989Sohal et al, , 1990b. Some of them are also known to change in cultures that are approaching the end of their proliferative lifespan (Doggett et al, 1992;Kodama et al, 1995;Kumar et al, 1992;Linskens et al, 1995).…”

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

et al. 1999

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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.

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“…Aerobic cells also generate highly reactive oxygen centered by-products because a small portion of the oxygen they consume is univalently reduced to the superoxide free radical (-0;) (Brawn and Fridovich, 1980;Foreman and Fischer, 1981). Superoxide, as well as other reactive oxygen species derived from it, can adversely influence a number of cellular processes via destabilizing effects resulting from oxidant-induced structural damage (So-ha1 and Allen, 1990). Free radical damage has been implicated in a variety of pathologies ranging from ischemic damage (McCord, 1985) to cellular transformation (Oberley andOberley, 1986, 1988).…”

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confidence: 99%

“…Free radical damage has been implicated in a variety of pathologies ranging from ischemic damage (McCord, 1985) to cellular transformation (Oberley andOberley, 1986, 1988). It is also a widely held view that free radicals play a role in the aging process Allen, 1986, 1990;Allen, 1990) although their precise role remains unclear. Superoxide dismutases (SOD) are the primary cellular defense against the potentially destructive reactions catalyzed by '0; and its derivatives (McCord and Fridovich, 1969;Brawn and Fridovich, 1980;Fridovich, 1989).…”

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Expression and regulation of superoxide dismutase activity in human skin fibroblasts from donors of different ages

Allen

Keogh

Gerhard

et al. 1995

Journal Cellular Physiology

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We have determined the activities, protein, and mRNA abundances as well as the level of transcriptional activation of two intracellular forms of the free radical metabolizing enzyme superoxide dismutase in 29 human skin fibroblast lines established from donors of different ages. SOD-1 (a copper and zinc containing form of SOD) and SOD-2 (a manganese containing form of the enzyme) activities were both observed to be significantly lower in cell lines derived from fetal skin than in lines established from postnatal skin (ages 17-94 years). The percent of total activity contributed by SOD-1 decreased in an age-associated manner from approximately 50% in the fetal lines to less than 20% in lines established from old tissue donors. All of the cell lines were screened to exclude the possibility that they contained a polymorphism known to influence SOD-2 activity. Northern blot analysis revealed three SOD-1 mRNA transcripts that were 0.5, 0.7, and 1.9 kb in length. Although SOD-1 protein abundance was lower in fetal lines than in lines derived from postnatal donors, SOD-1 mRNA abundance did not differ between fetal cells and cell lines derived from young donors. SOD-2 protein abundance and mRNA abundance were both significantly lower in fetal lines than in postnatal lines. No postnatal age-dependent differences were observed in any of the SOD-2 parameters examined. Nuclear run-on analysis revealed that fetal cell lines exhibited a lower level of transcriptional initiation for SOD-1 than postnatal lines. The transcription of SOD-2 was readily detected in postnatal lines, but undetectable in fetal lines. These results are consistent with multiple levels of control for SOD-1 expression and with a strong transcriptional influence on SOD-2 expression.

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Role of Free Radicals in Senescence

Cited by 3 publications

References 46 publications

Regulation of the Manganese Superoxide Dismutase and Inducible Nitric Oxide Synthase Gene in Rat Neuronal and Glial Cells

Regulation of the Manganese Superoxide Dismutase and Inducible Nitric Oxide Synthase Gene in Rat Neuronal and Glial Cells

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

Expression and regulation of superoxide dismutase activity in human skin fibroblasts from donors of different ages

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