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Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ER?/ER? balance in female mice.

ABSTRACT: AIMS: Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). METHODS AND RESULTS: Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR but not in SAMP. E2 is also known to increase NO by decreasing its catabolism by superoxide anion (O(2)(-)). Interestingly, E2 treatment decreased O(2)(-) production in young females, while increased O(2)(-) in aged ones. Furthermore, we observed that aging changed expression ratio of estrogen receptors (ER?/ER?) and levels of DNA methylation. Increased ratio ER?/ER? in aged females is associated to a lack of estrogen modulation of NO production and with a reversal in its antioxidant effect to a pro-oxidant profile. CONCLUSIONS: Together, our data suggest that aging has detrimental effects on E2-mediated benefits on NO bioavailability, partially by affecting the ability of E2 to induce up regulation of eNOS and decrease of O(2)(-). These modifications may be associated to aging-mediated modifications on global DNA methylation status, but not to a specific methylation at 5'flanking region of ER? gene.

SUBMITTER: Novensa L

PROVIDER: S-EPMC3178641 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice.

Novensà Laura L Novella Susana S Medina Pascual P Segarra Gloria G Castillo Nadia N Heras Magda M Hermenegildo Carlos C Dantas Ana Paula AP

PloS one 20110922 9

<h4>Aims</h4>Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM).<h4>Methods and results</h4>Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/N ...[more]

PMID: 21966501

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Project description:Food-provisioning of wildlife can facilitate reliable up-close encounters desirable by tourists and, consequently, tour operators. Food-provisioning can alter the natural behavior of an animal, encouraging adverse behavior (e.g. begging for food handouts), and affect the reproductive success and the viability of a population. Studies linking food-provisioning to reproductive success are limited due to the lack of long-term datasets available, especially for long-lived species such as marine mammals. In Bunbury, Western Australia, a state-licensed food-provisioning program offers fish handouts to a limited number of free-ranging bottlenose dolphins (Tursiops aduncus). Coupled with long-term historical data, this small (<200 individuals), resident dolphin population has been extensively studied for over ten years, offering an opportunity to examine the effect of food-provisioning on the reproductive success of females (ntotal?=?63; nprovisioned females?=?8). Female reproductive success was estimated as the number of weaned calves produced per reproductive years and calf survival at year one and three years old was investigated. The mean reproductive success of provisioned and non-provisioned females was compared using Bayes factor. We also used generalized linear models (GLMs) to examine female reproductive success in relation to the occurrence of food-provisioning, begging behavior and location (within the study area). Furthermore, we examined the influence of these variables and birth order and climatic fluctuations (e.g. El Niño Southern Oscillation) on calf survival. Bayes factor analyses (Bayes factor?=?6.12) and results from the best fitting GLMs showed that female reproductive success and calf survival were negatively influenced by food-provisioning. The negative effects of food-provisioning, although only affecting a small proportion of the adult females' population (13.2%), are of concern, especially given previous work showing that this population is declining.

Dataset Information

Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ER?/ER? balance in female mice.

Publications

Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice.

Similar Datasets

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