RNA modifications by oxidation: A novel disease mechanism?

Poulsen, Henrik Enghusen; Specht, Elisabeth; Broedbaek, Kasper; Henriksen, Trine; Ellervik, Christina; Mandrup-Poulsen, Thomas; Tonnesen, Morten; Nielsen, Peter E.; Andersen, Henrik U; Weimann, Allan

doi:10.1016/j.freeradbiomed.2012.01.009

Cited by 181 publications

(126 citation statements)

References 128 publications

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“…While oxidative damage is not the sole cause of biological aging, it is widely believed to be an important player in the aging process (Muller et al, 2007). Various oxidative damage markers are elevated or involved in age-related diseases such as diabetes (Monnier et al, 2006; Poulsen et al, 2012), cancer (Valko et al, 2006), neurodegenerative diseases (Nunomura et al, 2012; Poulsen et al, 2012) and cardiovascular disease (Gutierrez et al, 2006). Oxidative damage is caused by reactive oxygen species (ROS) unmitigated by antioxidants.…”

Section: Introductionmentioning

confidence: 99%

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

Aschbacher

O’Donovan

Wolkowitz

et al. 2013

Psychoneuroendocrinology

376

256

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Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.

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Section: Introductionmentioning

confidence: 99%

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

Aschbacher

O’Donovan

Wolkowitz

et al. 2013

Psychoneuroendocrinology

376

256

View full text Add to dashboard Cite

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“…In vivo, they are produced by respiration. 6 Outside the cell, they can be generated by mechanisms generally involving metallic ions. 7,8 Oxidation could also result from attacks by ozone, an atmospheric pollutant that rapidly reacts with RNA either in solution or in the solid state.…”

Section: Introductionmentioning

confidence: 99%

An efficient method for long-term room temperature storage of RNA

Fabre

Colotte²,

Luis³

et al. 2013

Eur J Hum Genet

113

110

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RNA is a tool used in many fields, from molecular and cellular biology to medicine and nanotechnology. For most of these uses, the integrity of RNA is required and must be maintained during storage. Even though freezing is currently the storage method of choice, the increasing number of samples to be stored and the costly use of a cold chain have highlighted the need for room temperature preservation methods. Here, we report a new room temperature technology that consists in drying RNA samples in the presence of a stabilizer in stainless steel minicapsules. These air-and water-tight capsules isolate RNA from the atmosphere and maintain an anhydrous and anoxic environment. Through the evaluation of RNA integrity over time at room temperature or 90 1C, we identified atmospheric humidity as a major deleterious factor. The degradation rate dependence in temperature fitted an Arrhenius model, with an activation energy of 28.5 kcal/mol and an extrapolated room temperature degradation rate of 3.2 10 À13 /nt/s (95% confidence interval: 2.3-4.2/nt/s). In these conditions, it is expected that an RNA molecule will be subjected to 0.7-1.3 cut every 1000 nucleotides per century. In addition, we showed that stored RNA is compatible for further analyses, such as reverse transcription-quantitative PCR. No significant change in the C q values was observed over a simulated period of several decades. At last, our data are consistent with a sequence-independent degradation rate of RNA in the solid state.

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“…However, it remains elusive whether oxidative damage to nucleic acids can link hyperthyroid diseases to such harmful effects on health. Focus has traditionally been on DNA oxidation but recently RNA oxidation has gained increasing attention due to its association with chronic disorders like Alzheimer's disease and diabetes mellitus [33]. Thus, the relationship between RNA oxidation and thyroid diseases might be an interesting new research field.…”

Section: Discussionmentioning

confidence: 99%

Systemic Oxidative Stress to Nucleic Acids Is Unaltered Following Radioiodine Therapy of Patients with Benign Nodular Goiter

et al. 2015

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Background: Little is known about the whole body oxidative stress burden following radioactive iodine (¹³¹I) therapy of thyroid diseases. Methods: We studied 17 patients with benign nodular goiter treated with ¹³¹I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine (normalized against the creatinine concentration) at baseline, and 7 and 21 days after rhTSH (not followed by ¹³¹I), and 7 and 21 days after ¹³¹I therapy, respectively. Results: The baseline urinary excretions of 8-oxoGuo and 8-oxodG were 2.20 ± 0.84 and 1.63 ± 0.70 nmol/mmol creatinine, respectively. We found no significant changes in the excretion of any of the metabolites, neither after rhTSH stimulation alone nor after ¹³¹I therapy. Also, no significant differences were found between the rhTSH group (low dose, median ¹³¹I: 152 MBq) and the non-rhTSH group (high dose, median ¹³¹I: 419 MBq; 8-oxoGuo: p = 0.66, 8-oxodG: p = 0.71). Conclusion: Systemic oxidative stress, as detected by nucleic acids metabolites in the urine, is not increased after thyroid stimulation with 0.1 mg of rhTSH, or after ¹³¹I therapy. Our method cannot quantify the oxidative stress induced locally in the thyroid gland, but the study supports that ¹³¹I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.

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RNA modifications by oxidation: A novel disease mechanism?

Cited by 181 publications

References 128 publications

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity

An efficient method for long-term room temperature storage of RNA

Systemic Oxidative Stress to Nucleic Acids Is Unaltered Following Radioiodine Therapy of Patients with Benign Nodular Goiter

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