Dynamic changes in maternal‒zygotic transition (MZT) require complex regulation of zygote formation, maternal transcript decay, embryonic genome activation (EGA), and cell cycle progression. Although these changes are well described, some key regulatory factors are still elusive. Sirtuin-1 (SIRT1), an NAD+-dependent histone deacetylase, is a versatile driver of MZT via its epigenetic and nonepigenetic substrates. This study focused on the dynamics of SIRT1 in early embryos and its contribution to MZT. A conditional SIRT1-deficient knockout mouse model was used, accompanied by porcine and human embryos. Embryos across mammalian species showed the prominent localization of SIRT1 in the nucleus throughout early embryonic development. Accordingly, SIRT1 interacts with histone H4 on lysine K16 (H4K16) in both mouse and human blastocysts. While maternal SIRT1 is dispensable for MZT, at least one allele of embryonic Sirt1 is required for early embryonic development around the time of EGA. This role of SIRT1 is surprisingly mediated via a transcription-independent mode of action.

• MeSH
• blastocysta metabolismus   MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj * genetika   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• myši knockoutované * MeSH
• myši MeSH
• prasata MeSH
• sirtuin 1 * metabolismus   genetika   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• zygota * metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics.

• MeSH
• acetylcholinesterasa genetika   MeSH
• butyrylcholinesterasa genetika   MeSH
• dospělí MeSH
• glutathion-S-transferasa fí genetika   MeSH
• glutathion MeSH
• glutathiontransferasa genetika   MeSH
• GPI-vázané proteiny genetika   MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus * MeSH
• katalasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malondialdehyd MeSH
• mladiství MeSH
• mladý dospělý MeSH
• organofosforové sloučeniny škodlivé účinky   MeSH
• oxidační stres genetika   MeSH
• sirtuin 1 genetika   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Kamerun MeSH
• Pákistán MeSH

The involvement of the mTOR system/enzyme sirtuin 1 (SIRT1) intracellular signaling system in the control of ovarian functions and its role in mediating hormonal action on the ovary has been proposed, but this hypothesis should be supported by a demonstrated influence of hormones on mTOR/SIRT1. Therefore, the aim of our in vitro experiments was to examine the effect of the known hormonal regulators of ovarian functions, such as follicle-stimulating hormone (FSH), oxytocin (OT) and insulin-like growth factor I (IGF-I), on mTOR/SIRT1. The accumulation of SIRT1 in porcine ovarian granulosa cells cultured with and without these hormones (at doses of 1, 10 or 100 ng.ml-1) was evaluated using immunocytochemistry. It was observed that the addition of FSH (at 10 ng.ml-1 but not at 1 or 100 ng/ml) and OT (at all tested doses) increased the expression of SIRT1 in ovarian cells. In addition, 100 ng.ml-1, but not at 1 or 10 ng.ml-1, of IGF-I decreased SIRT1 accumulation. Our observations are the first demonstration that hormones can directly regulate the ovarian mTOR/SIRT1 system and that this system could mediate the action of hormonal regulators on the ovary.

• MeSH
• apoptóza účinky léků   MeSH
• folikulární buňky cytologie   účinky léků   metabolismus   MeSH
• folikuly stimulující hormon farmakologie   MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• kultivované buňky MeSH
• ovarium cytologie   účinky léků   metabolismus   MeSH
• oxytocin farmakologie   MeSH
• prasata MeSH
• proliferace buněk účinky léků   MeSH
• sirtuin 1 biosyntéza   genetika   metabolismus   MeSH
• uterotonika farmakologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hyperbaric oxygen preconditioning (HBO-PC) has been proposed as a safe and practical approach for neuroprotection in ischemic stroke. However, it is not known whether HPO-PC can improve cognitive deficits induced by cerebral ischemia, and the mechanistic basis for any beneficial effects remains unclear. We addressed this in the present study using rats subjected to middle cerebral artery occlusion (MCAO) as an ischemic stroke model following HBO-PC. Cognitive function and expression of phosphorylated neurofilament heavy polypeptide (pNF-H) and doublecortin (DCX) in the hippocampus were evaluated 14 days after reperfusion and after short interfering RNA-mediated knockdown of sirtuin1 (Sirt1). HBO-PC increased pNF-H and DCX expression and mitigated cognitive deficits in MCAO rats. However, these effects were abolished by Sirt1 knockdown. Our results suggest that HBO-PC can protect the brain from injury caused by ischemia-reperfusion and that Sirt1 is a potential molecular target for therapeutic approaches designed to minimize cognitive deficits caused by cerebral ischemia.

• MeSH
• časové faktory MeSH
• chování zvířat * MeSH
• fosforylace MeSH
• hipokampus enzymologie   patofyziologie   MeSH
• hyperbarická oxygenace * MeSH
• infarkt arteria cerebri media enzymologie   patofyziologie   psychologie   terapie   MeSH
• kognice * MeSH
• kognitivní poruchy enzymologie   patofyziologie   prevence a kontrola   psychologie   MeSH
• modely nemocí na zvířatech MeSH
• neurofilamentové proteiny metabolismus   MeSH
• neuropeptidy metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• RNA interference MeSH
• sirtuin 1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The silent information regulator 1 (Sirt1) has been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles weak Notch loss-of-function phenotypes, and genetic interactions of Sirt1 with the components of the Notch pathway also suggest a positive role for Sirt1 in Notch signalling. Sirt1 is necessary for the efficient activation of enhancer of split [E(spl)] genes by Notch in S2N cells. Additionally, the Notch-dependent response of several E(spl) genes is sensitive to metabolic stress caused by 2-deoxy-d-glucose treatment, in a Sirt1-dependent manner. We found Sirt1 associated with several proteins involved in Notch repression as well as activation, including the cofactor exchange factor Ebi (TBL1), the RLAF/LAF histone chaperone complex and the Tip60 acetylation complex. Moreover, Sirt1 participates in the deacetylation of the CSL transcription factor Suppressor of Hairless. The role of Sirt1 in Notch signalling is, therefore, more complex than previously recognized, and its diverse effects may be explained by a plethora of Sirt1 substrates involved in the regulation of Notch signalling.

• MeSH
• buněčné linie MeSH
• deoxyglukosa farmakologie   MeSH
• Drosophila MeSH
• hmotnostní spektrometrie MeSH
• imunoprecipitace MeSH
• messenger RNA antagonisté a inhibitory   MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• receptory Notch genetika   metabolismus   MeSH
• represorové proteiny genetika   metabolismus   MeSH
• RNA interference fyziologie   MeSH
• signální transdukce účinky léků   genetika   MeSH
• sirtuin 1 genetika   metabolismus   MeSH
• transkripční faktory bHLH genetika   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Pregnane X receptor (PXR) is a major transcriptional regulator of xenobiotic metabolism and transport pathways in the liver and intestines, which are critical for protecting organisms against potentially harmful xenobiotic and endobiotic compounds. Inadvertent activation of drug metabolism pathways through PXR is known to contribute to drug resistance, adverse drug-drug interactions, and drug toxicity in humans. In both humans and rodents, PXR has been implicated in non-alcoholic fatty liver disease, diabetes, obesity, inflammatory bowel disease, and cancer. Because of PXR's important functions, it has been a therapeutic target of interest for a long time. More recent mechanistic studies have shown that PXR is modulated by multiple PTMs. Herein we provide the first investigation of the role of acetylation in modulating PXR activity. Through LC-MS/MS analysis, we identified lysine 109 (K109) in the hinge as PXR's major acetylation site. Using various biochemical and cell-based assays, we show that PXR's acetylation status and transcriptional activity are modulated by E1A binding protein (p300) and sirtuin 1 (SIRT1). Based on analysis of acetylation site mutants, we found that acetylation at K109 represses PXR transcriptional activity. The mechanism involves loss of RXRα dimerization and reduced binding to cognate DNA response elements. This mechanism may represent a promising therapeutic target using modulators of PXR acetylation levels. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

• MeSH
• acetylace MeSH
• aktivace transkripce * MeSH
• buňky Hep G2 MeSH
• DNA chemie   metabolismus   MeSH
• Escherichia coli genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• klonování DNA MeSH
• lidé MeSH
• luciferasy genetika   metabolismus   MeSH
• lysin chemie   metabolismus   MeSH
• molekulární modely MeSH
• multimerizace proteinu MeSH
• mutageneze cílená MeSH
• posttranslační úpravy proteinů * MeSH
• rekombinantní proteiny chemie   genetika   metabolismus   MeSH
• reportérové geny MeSH
• responzivní elementy MeSH
• sekundární struktura proteinů MeSH
• sirtuin 1 genetika   metabolismus   MeSH
• steroidní receptory chemie   genetika   metabolismus   MeSH
• strukturní homologie proteinů MeSH
• transkripční faktory p300-CBP genetika   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Stress-induced fibroblast senescence is thought to contribute to skin aging. Ultraviolet light (UV) radiation is the most potent environmental risk factor in these processes. An Epilobium angustifolium (EA) extract was evaluated for its capacity to reverse the senescent response of normal human dermal fibroblasts (NHDF) in vitro and to exhibit skin photo-protection in vivo. The HPLC-UV-MS analysis of the EA preparation identified three major polyphenol groups: tannins (oenothein B), phenolic acids (gallic and chlorogenic acids) and flavonoids. EA extract increased the cell viability of senescent NHDF induced by serum deprivation. It diminished connective tissue growth factor and fibronectin gene expressions in senescent NHDF. Down-regulation of the UV-induced release of both matrix metalloproteinase-1 and -3 and the tissue inhibitor of matrix metalloproteinases-1 and -2, and also down-regulation of the gene expression of hyaluronidase 2 were observed in repeatedly UV-irradiated NHDF after EA extract treatment. Interestingly, EA extract diminished the down-regulation of sirtuin 1 dampened by UV-irradiation. The application of EA extract using a sub-irritating dose protected skin against UV-induced erythema formation in vivo. In summary, EA extract diminished stress-induced effects on NHDF, particularly on connective tissue growth factor, fibronectin and matrix metalloproteinases. These results collectively suggest that EA extract may possess anti-aging properties and that the EA polyphenols might account for these benefits.

• MeSH
• dítě MeSH
• dospělí MeSH
• down regulace účinky léků   účinky záření   MeSH
• Epilobium chemie   MeSH
• erytém farmakoterapie   etiologie   MeSH
• extracelulární matrix účinky léků   metabolismus   účinky záření   MeSH
• fenotyp MeSH
• fibroblasty cytologie   účinky léků   metabolismus   účinky záření   MeSH
• fibronektiny genetika   MeSH
• GPI-vázané proteiny genetika   MeSH
• hyaluronoglukosaminidasa genetika   MeSH
• kůže cytologie   účinky léků   účinky záření   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• molekuly buněčné adheze genetika   MeSH
• radioprotektivní látky chemie   farmakologie   terapeutické užití   MeSH
• regulace genové exprese účinky léků   účinky záření   MeSH
• rostlinné extrakty chemie   farmakologie   terapeutické užití   MeSH
• růstový faktor pojivové tkáně genetika   MeSH
• sirtuin 1 genetika   MeSH
• stárnutí buněk účinky léků   účinky záření   MeSH
• stárnutí kůže účinky léků   účinky záření   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH