An investigation of DNA excision repair capacity in human CD4+ T cell clones as a function of age in vitro

Annett, Kathryn; Hyland, Paul; Duggan, Orla; Barnett, Christopher R.; Barnett, Yvonne

doi:10.1016/j.exger.2003.09.028

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…Published papers have reported a decrease in other markers of T cell integrity with age. The DNA repair capacity in T cells in vitro has been shown to decline with age, revealed in previous studies by this group [6,7]. Furthermore, Heat Shock Protein activity has been demonstrated to decline in response to age making the body more susceptible to stress-induced damage [17,18].…”

Section: Discussionmentioning

confidence: 95%

“…In vivo levels of antioxidants and DNA repair mechanisms represent two types of T cell defence systems that can counteract ROS-induced DNA damage [5]. An age-related decline of DNA repair capacities has been previously reported in CD4 + TCCs cultured in vitro in 20% O 2 tension [6,7]. Here, we set out to determine the potential of the antioxidants 2-phenyl-1,2-benzisoselenazol-3 (2H)-one (ebselen) and N-acetyl L-cysteine (NAC) to protect T cells from the damaging effects of ROS.…”

Section: Introductionmentioning

confidence: 99%

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An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

Marthandan¹,

Hyland

Pawelec

et al. 2013

Immun Ageing

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BackgroundThe research literature has documented age-related increases in genetic damage, including oxidative DNA damage, in human T lymphocytes, in vitro and ex vivo. Such damage has the potential to interfere with the ability of the T cells to proliferate at times when they need to, such as when antigen challenged. The consequence of this could be a sub-optimal immune response in vivo.Context and purposeThe purpose of the research reported in this paper was to investigate the impact of two antioxidants, which can be administered in vivo, Ebselen and N-acetyl L-cysteine, on the age-related increase in genetic damage, and on T cell proliferation and lifespan. In vitro human T cell clones, ex vivo peripheral blood mononuclear cells or T cells were supplemented with different concentrations of antioxidants, under standard conditions and for different periods of time. A range of assays were then applied in order to determine any impact of the antioxidants.Results30 μM ebselen or 7.5 mM N-acetyl L-cysteine supplementation resulted in a significantly higher intracellular GSH: GSSG ratio. This increased ratio was accompanied by reduced levels of oxidative DNA damage in established CD4+ human T cell clones, from a young or a middle-aged donor. Additionally, cultures of primary human peripheral blood mononuclear cells and CD4+ T cells from donors aged 25–30 or 55–60 years were also supplemented with these agents. Cells from all sources exhibited increased proliferation, and in the case of the T cell clones, an increase in cumulative population doublings. Neither ebselen nor N-acetyl L-cysteine had such effects on clones supplemented from the midpoint of their in vitro lifespan.ConclusionsEbselen and N-acetyl L-cysteine, under certain conditions, may have anti-immunosenescent potential in T cells in in vitro clonal and ex vivo polyclonal culture models.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

Marthandan¹,

Hyland

Pawelec

et al. 2013

Immun Ageing

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“…Furthermore, replicative aging may vary between cell lines, depending on the cell donor. For example, a decline in NER with increasing passages was documented for lymphocytes derived from two different donors but not in the lymphocytes from the third donor ( 51 ).…”

Section: Age-related Changes In Nucleotide Excision Repair (Ner)mentioning

confidence: 96%

Changes in DNA repair during aging

Gorbunova

Seluanov

Mao

et al. 2007

Nucleic Acids Research

336

223

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DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old.

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“…However, the sensitivity to these agents was not increased by the SFN‐i treatment (data not shown). The additionally tested agents were reported to have actions on DNA molecules different from that of UV‐C: mitomycin C is a cross‐linking agent, X‐ray irradiation induces double‐ and singlestrand breaks and oxidative damage and hydrogen peroxide induces oxidative damage (21–23). Thus, Sfn is possibly involved specifically in the resistance to UV‐C, at least among the DNA‐damaging agents tested here.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Human Small Fragment Nuclease in the Resistance of Human Cells to UV‐C‐induced Cell Death^¶

Ito

Kita

Zhal

et al. 2004

Photochem & Photobiology

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Human small fragment nuclease (Sfn) is one of the cellular proteins that were reported to degrade small, single‐stranded DNA and RNA. However, the biological role of Sfn in cellular response to various stressors such as UV‐C (mainly 254 nm wavelength ultraviolet ray) remains unclear. We have examined whether modulation of human SFN gene expression affects cell survival capacity against UV‐C‐induced cell death, analyzing colony survival ability in UV‐C‐sensitive human RSa cells treated with short double‐stranded RNA (siRNA) specific for SFN messenger RNA (mRNA). The expression levels of SFN mRNA in the siRNA‐treated RSa cells decreased to about 15% compared with those in the control siRNA‐treated cells. The siRNA‐treated RSa cells showed lower colony survival and higher activity of caspase‐3 after UV‐C irradiation than the control siRNA‐treated RSa cells. Furthermore, the removal capacity of cyclobutane pyrimidine dimers (CPD) in the siRNA‐treated RSa cells decreased compared with the control siRNA‐treated RSa cells. There was no difference in the colony survival and CPD removal capacity after UV‐C irradiation between the control siRNA‐treated RSa cells and mock‐treated RSa cells. These results suggest that SFN expression is involved in resistance of RSa cells to UV‐C‐induced cell death through the roles it plays in the DNA repair process.

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An investigation of DNA excision repair capacity in human CD4+ T cell clones as a function of age in vitro

Cited by 12 publications

References 24 publications

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

Changes in DNA repair during aging

Involvement of Human Small Fragment Nuclease in the Resistance of Human Cells to UV‐C‐induced Cell Death^¶

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An investigation of DNA excision repair capacity in human CD4+ T cell clones as a function of age in vitro

Cited by 12 publications

References 24 publications

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

Changes in DNA repair during aging

Involvement of Human Small Fragment Nuclease in the Resistance of Human Cells to UV‐C‐induced Cell Death¶

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Product

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Involvement of Human Small Fragment Nuclease in the Resistance of Human Cells to UV‐C‐induced Cell Death^¶