scholarly journals Stress hormones promote DNA damage in human oral keratinocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vitor Bonetti Valente ◽  
Diovana de Melo Cardoso ◽  
Giseli Mitsuy Kayahara ◽  
Giovana Barros Nunes ◽  
Kellen Cristine Tjioe ◽  
...  
Keyword(s):  
Dna Damage ◽  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Stress Hormones ◽  
Oral Keratinocytes ◽  
Dna Breaks ◽  
Genotoxic Effects ◽  
Beta Adrenergic ◽  
Pre Treatment ◽  
Antagonist Ru486

AbstractChronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

scholarly journals The influence of stress hormones and aggression on cooperative behaviour in subordinate meerkats

2017 ◽  
Vol 284 (1863) ◽  
pp. 20171248 ◽  
Author(s):  
Ben Dantzer ◽  
Ines Braga Goncalves ◽  
Helen C. Spence-Jones ◽  
Nigel C. Bennett ◽  
Michael Heistermann ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Treatment Effects ◽  
Stress Hormones ◽  
Cooperative Behaviour ◽  
Food Provisioning ◽  
Stress Hormone ◽  
Suricata Suricatta

In cooperative breeders, aggression from dominant breeders directed at subordinates may raise subordinate stress hormone (glucocorticoid) concentrations. This may benefit dominants by suppressing subordinate reproduction but it is uncertain whether aggression from dominants can elevate subordinate cooperative behaviour, or how resulting changes in subordinate glucocorticoid concentrations affect their cooperative behaviour. We show here that the effects of manipulating glucocorticoid concentrations in wild meerkats ( Suricata suricatta ) on cooperative behaviour varied between cooperative activities as well as between the sexes. Subordinates of both sexes treated with a glucocorticoid receptor antagonist (mifepristone) exhibited significantly more pup protection behaviour (babysitting) compared to those treated with glucocorticoids (cortisol) or controls. Females treated with mifepristone had a higher probability of exhibiting pup food provisioning (pup-feeding) compared to those treated with cortisol. In males, there were no treatment effects on the probability of pup-feeding, but those treated with cortisol gave a higher proportion of the food they found to pups than those treated with mifepristone. Using 19 years of behavioural data, we also show that dominant females did not increase the frequency with which they directed aggression at subordinates at times when the need for assistance was highest. Our results suggest that it is unlikely that dominant females manipulate the cooperative behaviour of subordinates through the effects of aggression on their glucocorticoid levels and that the function of aggression directed at subordinates is probably to reduce the probability they will breed.

scholarly journals Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells

2020 ◽  
Vol 21 (6) ◽  
pp. 2250 ◽  
Author(s):  
Rocio Lamboy-Caraballo ◽  
Carmen Ortiz-Sanchez ◽  
Arelis Acevedo-Santiago ◽  
Jaime Matta ◽  
Alvaro N.A. Monteiro ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Adrenergic Receptors ◽  
Stress Hormones ◽  
Ovarian Cancer Cells ◽  
Dna Integrity ◽  
Chemotherapy Response ◽  
Dna Breaks ◽  
Strand Breaks ◽  
Β Adrenergic Receptors

Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by β-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of β-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells.

Abstract 780: Atorvastatin Activates A Novel Nbs1-dependent Mechanism Of Accelerating Dna Repair In Atherosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Melli M Mahmoudi ◽  
Isabelle C Gorenne ◽  
John R Mercer ◽  
Nichola L Figg ◽  
Martin R Bennett
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oxidant Stress ◽  
Dna Breaks ◽  
Western Blots ◽  
Dna Damage And Repair ◽  
Pre Treatment ◽  
Reactive Oxidant ◽  
Sirna Knockdown ◽  
Dependent Mechanism

There is increasing evidence that reactive oxidant species (ROS) and DNA damage promote the development and complications of atherosclerosis. Although statin therapy reduces both ROS and DNA damage in atherosclerosis, the mechanism of this effect is unknown. We first examined expression of DNA damage and repair markers in vascular smooth muscle cells (VSMCs) of human atherosclerotic plaques. With increasing disease severity, there was increased VSMC expression of the DNA repair markers P-ATM/ATR substrate and P-H2AX from 2.7%±2.2 and 0.5±0.71 [mean±SEM] (AHA Grade I/II), to 21%±3.5 and 36.5±2.1 (Grade III) lesions, and 86.5%±0.7 and 69.3±7.6 (Grade IV/V). Cultured plaque VSMCs also showed a 1.5 fold increased oxidant stress; a 4.4 fold increased double-stranded DNA breaks, and expression of P-H2AX by Western blots. ROS analogues induced a robust DNA damage response in VSMCs, characterised by lengthening of tails on COMET assay, and activation of ATM and P-H2AX, with completion of repair by 6 hours. Atorvastatin pre-treatment accelerated DNA repair by approximately 2 hours without inhibiting ROS induction or DNA damage, and markedly accelerated the kinetics of nibrin (NBS-1) and P-H2AX activation, both proteins recruited to sites of DNA damage, by preventing degradation of NBS-1. Atorvastatin induced phosphorylation of HDM2, an E3 ligase and putative regulator of NBS-1 stability, and siRNA knockdown of HDM2 replicated the effect of atorvastatin on NBS-1. The ability of atorvastatin to accelerate repair was completely dependent upon NBS-1, as atorvastatin was ineffective in cells either null or expressing constitutively active NBS-I. In summary, we have demonstrated a novel NBS-1-dependent mechanism by which statins accelerate DNA repair in atherosclerosis, through HDM2 phosphorylation and stabilisation of NBS-1. We believe that both NBS-1 and HDM2 are critical to DNA repair in atherosclerosis.

The effects of the glucocorticoid receptor antagonist RU486 and phospholipase A2 inhibitor quinacrine on acoustic injury of the mouse cochlea

2007 ◽  
Vol 413 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Yuki Hirose ◽  
Keiji Tabuchi ◽  
Keiko Oikawa ◽  
Hidekazu Murashita ◽  
Shuhei Sakai ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Phospholipase A2 ◽  
Receptor Antagonist ◽  
Phospholipase A2 Inhibitor ◽  
Antagonist Ru486

scholarly journals Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced behavioural sensitisation

PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0176156 ◽  
Author(s):  
Emilia M. Lefevre ◽  
Gregory A. Medley ◽  
Timothy Reeks ◽  
Suzy Alexander ◽  
Thomas H. J. Burne ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Mk 801 ◽  
Behavioural Sensitisation ◽  
Antagonist Ru486

scholarly journals Bridging a Gap between Cr(VI)-Induced Oxidative Stress and Genotoxicity in Lettuce Organs after a Long-Term Exposure

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Cristina Monteiro ◽  
Sara Sario ◽  
Rafael Mendes ◽  
Nuno Mariz-Ponte ◽  
Sónia Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Crop Production ◽  
Antioxidant Activities ◽  
Dependent Manner ◽  
Dna Breaks ◽  
Arable Soils ◽  
Genotoxic Effects ◽  
Organ Specific

Chromium (Cr) contamination in arable soils and irrigating water remains a priority, particularly due to the challenges posed to crop production and food safety. Long-term Cr(VI) effects remain less addressed than short-term ones, particularly regarding organ-specific genotoxic profiles. Here we used the crop Lactuca sativa growing in a protected horticultural system and irrigated for 21 days with Cr(VI) (up to 200 mg/L). Besides the oxidative stress, the genotoxicity was evaluated. Shoots and roots showed distinctive oxidative stress status and genotoxic effects, in a dose-dependent manner. While 50 mg/L stimulated antioxidant activities and no major genotoxic effects were found, plants exposed to ≥150 showed an increase of oxidative disorders, together with cytostatic and DNA damage effects, and some mitotic impairment. Leaves showed less oxidative signs at 50 mg/L, while at 150/200 mg/L the antioxidant battery was stimulated. In Cr treated plants, the highest dose increased the DNA damage, reinforcing the idea that DNA breaks were related to mitotic disorders in higher doses. In conclusion, long-term exposure data show a highly responsive root, with a quadratic response meaning higher defenses at lower Cr doses, and higher oxidative and DNA damage and cytostatic effect at a higher dose.

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