The effects of carnosine on oxidative DNA damage levels and in vitro lifespan in human peripheral blood derived CD4+T cell clones

Hyland, Paul; Duggan, Orla; Hipkiss, Alan R.; Barnett, Christopher R.; Barnett, Yvonne

doi:10.1016/s0047-6374(00)00211-6

Cited by 33 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis fits with the observation that profilin-1 -and profilin-1-interacting proteins- are highly sensitive to oxidative damage. It also agrees with the documented increased levels of oxidative DNA damage found in late-passage T-cell clones [37,38]. However, to date, alterations of expression and activity of these redox-sensitive proteins, including profilin-1, in ageing remains unexplored.…”

Section: Discussionsupporting

confidence: 87%

SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term culture identifies human profilin-1 as a potential bio-marker of immunosenescence

Mazzatti

Pawelec

Longdin³

et al. 2007

Proteome Sci

View full text Add to dashboard Cite

Background: The adaptive immune response requires waves of T-cell clonal expansion on contact with pathogen and elimination after clearance of the source of antigen. However, lifelong persistent infections with common viruses cause chronic antigenic stimulation which takes its toll on adaptive immunity in late life. Chronic antigenic stress results in deregulation of the T-cell response and accumulation of anergic cells. Longitudinal studies of the elderly show that this impacts on survival. Identifying the nature of the defects in chronically-stimulated T-cells and protein bio-markers of these dysfunctional cells would help to understand age-associated compromised T-cell function (immunosenescence) and facilitate the development of targeted intervention strategies.

show abstract

Section: Discussionsupporting

confidence: 87%

SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term culture identifies human profilin-1 as a potential bio-marker of immunosenescence

Mazzatti

Pawelec

Longdin³

et al. 2007

Proteome Sci

View full text Add to dashboard Cite

show abstract

“…Of note, methylglyoxal, an endogenous metabolite accumulating in diabetes, can be neutralized by carnosine48. Even anti-ageing effects in T cells extending the lifespan under physiological oxygen tension have been described49. Additional supportive in vivo data comes e.g.…”

Section: Discussionmentioning

confidence: 98%

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Albrecht

Schilperoort

Zhang

et al. 2017

Sci Rep

111

View full text Add to dashboard Cite

We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman’s capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes.

show abstract

“…It has been shown to prevent bleomycin-induced lung injury [4], inhibit the growth of neoplastic cells [5], delay diabetic deterioration [6], [7], contribute to the improvement of Alzheimer's disease (AD) [8], and possess anti-aging activities [3], [9], [10]. Earlier reports also indicated that carnosine supplementation could regulate immune function, such as extending the lifespan of human CD4 + T cells [11], modulating immune response of rabbits against Schistosoma mansoni antigens and regulating the functions of neutrophils [12], [13]. Underlying mechanism of these effects was suggested to be related with the antioxidative property of carnosine [14].…”

Section: Introductionmentioning

confidence: 99%

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Tsoi

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.

show abstract

The effects of carnosine on oxidative DNA damage levels and in vitro lifespan in human peripheral blood derived CD4+T cell clones

Cited by 33 publications

References 30 publications

SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term culture identifies human profilin-1 as a potential bio-marker of immunosenescence

SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term culture identifies human profilin-1 as a potential bio-marker of immunosenescence

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Contact Info

Product

Resources

About