Err gamma

The endocrine disruptor Bisphenol A (BPA), a widely employed molecule in plastics, has been shown to affect several biological processes in vertebrates, mostly via binding to nuclear receptors. Neurodevelopmental effects of BPA have been documented in vertebrates and linked to neurodevelopmental disorders, probably because some nuclear receptors are present in the vertebrate brain. Similarly, endocrine disruptors have been shown to affect neurodevelopment in marine invertebrates such as ascidians, mollusks or echinoderms, but whether invertebrate nuclear receptors are involved in the mode-of-action is largely unknown...

Chromosomal maintenance 1 (CRM1) inhibitors display antihypertrophic effects and control protein trafficking between the nucleus and the cytoplasm. PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1alpha) is a type of transcriptional coactivator that predominantly resides in the nucleus and is downregulated during heart failure. NT-PGC-1α is an alternative splicing variant of PGC-1α that is primarily distributed in the cytoplasm. We hypothesized that the use of a CRM1 inhibitor could shuttle NT-PGC-1α into the nucleus and activate PGC-1α target genes to potentially improve cardiac function in a mouse model of myocardial infarction (MI)...

Several journal reports, reviews, and commentaries over the last 20-25 years have pointed out the controversy attached to 17β-estradiol's inhibitory or stimulatory influence on hair follicle growth/cycling citing rodent (murine) and human results. While 17β-estradiol is the most potent sex steroid hormone in the body and has almost equal affinity for estrogen receptor (ER) alpha (α) and beta (β), there appears to be specific ER-mediated effects on scalp hair follicles/growth, etc. Additionally, the newly discovered G protein-coupled estrogen receptor (GPR30 or GPER) and the orphan receptor, estrogen-related receptor (ERR) gamma (γ), in skin and other tissue sites have potential impacts of how estrogens via these receptors may alter scalp hair characteristics, but this remains to be elucidated...

Recently an increasing trend in skin cancer rates has been observed in various populations including those exposed to different radiation types. Risk and dose-response following prolonged radiation exposure remain unclear. The present study was aimed to assess skin melanoma (SM) and non-melanoma skin cancer (NMSC) incidence risks in a cohort of workers occupationally exposed to ionizing radiation at low dose rates over prolonged periods. The study cohort included workers of a Russian nuclear production facility, Mayak Production Association (PA), who were first employed in 1948-1982 and followed up till the end of 2013 (the total of 22,377 individuals with 25% of females)...

In obesity-linked insulin resistance, oxidative stress in adipocytes leads to lipid peroxidation and subsequent carbonylation of proteins by diffusible lipid electrophiles. Reduction in oxidative stress attenuates protein carbonylation and insulin resistance, suggesting that lipid modification of proteins may play a role in metabolic disease, but the mechanisms remain incompletely understood. Herein, we show that in vivo , diet-induced obesity in mice surprisingly results in preferential carbonylation of nuclear proteins by 4-hydroxy- trans -2,3-nonenal (4-HNE) or 4-hydroxy- trans -2,3-hexenal (4-HHE)...

BACKGROUND: Orphan nuclear receptors ERRα, ERRβ and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERRα, ERRγ and less about ERRβ is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins...

Adrenergic stimulation of brown adipose tissue (BAT) induces acute and long-term responses. The acute adrenergic response activates thermogenesis by uncoupling oxidative phosphorylation and enabling increased substrate oxidation. Long-term, adrenergic signaling remodels BAT, inducing adaptive transcriptional changes that expand thermogenic capacity. Here, we show that the estrogen-related receptors alpha and gamma (ERRα, ERRγ) are collectively critical effectors of adrenergically stimulated transcriptional reprogramming of BAT...

Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1 alpha (PGC-1α)...

Mortality from circulatory disease (CD), ischemic heart disease (IHD) and cerebrovascular disease (CeVD) was investigated in relationship to cumulative doses of external gamma radiation and internal alpha radiation to the liver from deposited plutonium over long follow-up periods in two large cohorts of nuclear workers: the Russian Mayak Worker Cohort (MWC) and the UK Sellafield Worker Cohort (SWC). The MWC comprised 22,374 workers (74.6% males) with 5,123 CD deaths registered during 842,538 person-years of follow-up, while the SWC comprised 23,443 workers (87...

OBJECTIVE: To examine specific molecular mechanisms involved in modulating hepatic lipogenesis and mitochondria biogenesis signals by Lithospermum erythrorhizon (gromwell) root extract. METHODS: Stable cell lines with luciferase reporter constructs were generated to examine sterol regulatory element binding protein 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1) α promoter activity and estrogen-related receptor (ERR) α response element activity...

In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis)...

Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...

BACKGROUND: Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. METHODS AND RESULTS: Cardiac-specific SIRT1 knockout (SIRT1KO ) mice were generated using Cre-loxP system. SIRT1KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism...

Estrogen-related receptor alpha (ERRα), the first orphan nuclear receptor discovered, is crucial for the control of cellular energy metabolism. ERRα and its coactivator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), are required for rapid energy production in response to environmental challenges. They have been implicated in the etiology of metabolic disorders such as type 2 diabetes and metabolic syndrome. ERRα also plays a role in the pathogenesis of breast cancer. Identification of compounds that modulate ERRα signaling may elucidate environmental factors associated with these diseases...

AIM: To assess mortality from circulatory diseases (CD) in a cohort of workers exposed occupationally to chronic radiation in relation to external and internal exposure, by taking into account known non-radiation risk factors (RFs), such as smoking (including smoking index), alcohol consumption, hypertension, and body mass index. SUBJECTS AND METHODS: Mortality from CD (ICD-10: I00 - I99) was studied in a cohort of 22,377 nuclear power plant («Mayak» Production Association) workers exposed occupationally to chronic radiation...

Estrogen-related receptor (ERR) is a member of the nuclear receptor superfamily that has strong homology with estrogen receptor (ER) α. Despite the lack of endogenous ligands, ERR serves as transcription factors through their constitutively active structure with or without interaction with ERα. Among the three subtypes of ERR (α, β, and γ), ERRγ is highly expressed in brain, but the distribution of ERRγ is poorly characterized. Therefore, we investigated ERRγ immunoreactivity throughout the rostro-caudal axis in rat brain...

INTRODUCTION: We present a Trajectory-based Volumetric Modulated Arc Therapy (TVMAT) technique for Stereotactic Radiosurgery (SRS) that takes advantage of a modern linacs ability to modulate dose rate and move the couch dynamically. In addition, we investigate the quality of the developed TVMAT method and the dosimetric accuracy of the technique. METHODS: The main feature of the TVMAT technique is a standard beam trajectory formed by dynamic motion of the treatment couch and the linac gantry...

INTRODUCTION: The progressive forms of inflammatory external root resorption (IERR) and replacement external root resorption (RERR) are serious complications and the main causes of tooth loss after replantation. This study aimed to investigate the expression pattern of inflammatory molecules in extracted human teeth presenting with external root resorption (ERR) after replantation. METHODS: Root fragments from 22 teeth showing IERR and 20 teeth with RERR were triturated using a homogenizer to extract inflammatory molecules...

We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERRγ but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERRγ over the ERRα, -β, and ERα. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds...

Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0...