Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis

Fouquerel, Elise; Barnes, Ryan; Uttam, Shikhar; Watkins, Simon C.; Bruchez, Marcel P.; Opresko, Patricia L.

doi:10.1016/j.molcel.2019.04.024

Cited by 200 publications

(238 citation statements)

References 81 publications

(101 reference statements)

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“…Although we report TL shortening at 18 months of age in both brain and heart tissue, previous research using zebrafish has not observed age-dependent differences in TL until fish are at least 2 years of age (41,70).Furthermore, others have shown no TL effect of age in the brain of zebrafish (39). Failure to detect telomere shortening in brain tissues could be a consequence of the lower rate of cell renewal and neurogenesis in the adult brain compared to heart making detection difficult (39,63,69).The lack of consistency in zebrafish findings highlights possible differences in the technique used to assess telomere length, on the rate of telomere attrition between strains (40,41) and animal facilities, which should all be carefully considered. Furthermore, we have combined data from a sibling populations of young and ageing zebrafish, thus allowing for samples to be processed simultaneously, which assures similar storage time and reagents used, critical consideration for the study of telomere biology (71).…”

Section: Discussionmentioning

confidence: 48%

“…When this peak is weakened by stress-related hormones (25,41,56) it may diminish their ability to counteract injuries thus leading to shorter telomeres and the associated increased risk of cardiomyopathies. However, our research cannot rule out a telomerase-independent process resulting from a chronically activated HPI axis, such as the postulated direct effect of reactive oxygen species (63). Nonetheless, the present investigation shows that zebrafish are a promising animal to model cardiomyopathies in ageing individuals.…”

Section: Discussionmentioning

confidence: 65%

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Stress reactivity elicits a tissue-specific reduction in telomere length in ageing zebrafish (Danio rerio)

Evans

Torres-Pérez

Petrazzini

et al. 2020

Preprint

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Telomere length reflects cellular ageing. Increased telomere shortening in leukocytes is associated with a range of neurodegenerative and cardiovascular diseases, the onset and progression of which may be mediated by behavioural traits such as anxiety and stress reactivity. However, the effects of the hypothalamus-pituitary-adrenal axis stress response are shown to be tissue specific. As such, leukocyte telomere length may not give an accurate measure of the relationship between stress-reactivity and telomere length in disease relevant tissues. To test the hypothesis that stress-reactivity contributes to age-related telomere shortening in a tissue specific manner, we examined the correlation between telomere length in heart and brain tissue and stress-reactivity in a population of young (6-9 month) and ageing (18 month) zebrafish. Stress-reactivity was assessed by tank diving, a zebrafish version of the rodent open-field test, and through gene expression. Telomere length was assessed using quantitative polymerase chain reaction. We show that ageing zebrafish have shorter telomeres in both heart and brain. Telomere length is inversely related to stress-reactivity in heart but not brain of ageing individuals. These data support the hypotheses that an anxious predisposition contributes to telomere shortening in heart tissue, and by extension age-related heart disease, and that stress-reactivity contributes to age-related telomere shortening in a tissue-specific manner.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 65%

Stress reactivity elicits a tissue-specific reduction in telomere length in ageing zebrafish (Danio rerio)

Evans

Torres-Pérez

Petrazzini

et al. 2020

Preprint

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“…Our test results of SOD and MDA found that SMCs in different dose groups can increase the SOD value of cells treated with ox-LDL and decrease the MDA value. SOD and MDA are classic indicators of oxidative stress evaluation, and there are currently reports in the literature that oxidative stress can promote cellular senescence [42][43][44]. Studies show that oxidative stress accelerate telomere shortening or dysfunction and telomere shortening suppresses cancer by triggering senescence in normal cells [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Shenqi Maixintong Capsule against ox‐LDL‐Induced Injury in RAW264.7 Macrophages

Liang

Cai

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Shenqi Maixintong capsule (SMC), a traditional Chinese medicine compound, exerts various therapeutic effects, including nourishing one’s vitality, improving blood circulation, regulating vital energy, and promoting coronary circulation. Studies have demonstrated that SMC could effectively alleviate atherosclerosis (AS) and delay its development. However, the effect of SMC on lipid metabolism remains unclear. Herein, we investigated the mechanism of SMC on lipid metabolism of RAW264.7 cells induced by oxidized low-density lipoprotein (ox-LDL). Drug-containing serum was prepared by intragastric administration of SD (Sprague Dawley) rats. RAW264.7 cells were transformed into foam cells with 25 mg/L ox-LDL. SMC-treated rat serum increased the survival rate of ox-LDL-induced RAW264.7 cells. Oil Red staining, total cholesterol, and free cholesterol detection data showed that the intermediated dose of SMC had the best effect on reducing the lipid accumulation, lipid droplets, intracellular cholesterol, and total cholesterol content of RAW264.7 cells. The results of western blotting showed that the expression of ABCA1, ABCG1, LXRα, PPARγ, and peroxisome proliferation-activated receptor alpha (PPARα) was increased by SMC, and proprotein convertase subtilisin/kexin type 9 (PCSK9) was reduced, which promoted reverse cholesterol transport (RCT) of RAW264.7 cells and inhibited foam cell formation. Furthermore, SOD and MDA data indicated that SMC could reduce the senescence of RAW264.7 cells. These findings suggest that SMC might prevent ox-LDL-induced damage of macrophages in AS patients by improving cell viability and slowing down lipid accumulation and senescence.

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“…Reactive oxygen species (ROS) modifies DNA bases, most commonly resulting in 8-oxoguanine (8-oxoG) and thymine glycol (Tg) (125). If not repaired, 8-oxoG induces GC-TA transversion mutations as well as single-strand or double-strand breaks, leading to genomic instability (126). Tg is the most prevalent oxidative product of thymine, responsible for 10 -20% of ionizing radiation-induced genomic damage (127).…”

Section: Telomere Proteins and Their Role In The Genome-wide Responsementioning

confidence: 99%

Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress

Barcenilla

Shippen

2019

Journal of Biological Chemistry

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Edited by Patrick Sung The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate terminal DNA sequences and the ability to distinguish chromosome ends from damaged DNA. Here we consider the multifaceted functions of factors recruited to perpetuate and stabilize telomeres. We discuss recent theories for how telomere factors evolved from existing cellular machineries and examine their engagement in nontelomeric functions such as DNA repair, replication, and transcriptional regulation. We highlight the remarkable versatility of protection of telomeres 1 (POT1) proteins that was fueled by gene duplication and divergence events that occurred independently across several eukaryotic lineages. Finally, we consider the relationship between oxidative stress and telomeres and the enigmatic role of telomere-associated proteins in mitochondria. These findings point to an evolving and intimate connection between telomeres and cellular physiology and the strong drive to maintain chromosome integrity.

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Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis

Cited by 200 publications

References 81 publications

Stress reactivity elicits a tissue-specific reduction in telomere length in ageing zebrafish (Danio rerio)

Stress reactivity elicits a tissue-specific reduction in telomere length in ageing zebrafish (Danio rerio)

Protective Effect of Shenqi Maixintong Capsule against ox‐LDL‐Induced Injury in RAW264.7 Macrophages

Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress

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