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1.
Endocr Res ; 49(2): 106-116, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38597376

RESUMEN

BACKGROUND: Phytoestrogens have been praised for their beneficial health effects, whereas synthetic xenoestrogens have been connected to ailments. AIMS: To ascertain whether the toxicities of natural and synthetic estrogens differ, we examined the potent phytoestrogen 8-prenylnaringenin (8-PN), the common synthetic xenoestrogen tartrazine, and the physiological estrogen 17ß-estradiol (E2). METHODS: These three compounds were tested for cytotoxicity, cell proliferation and genotoxicity in human HepG2 and rat H4IIE hepatoma cells. RESULTS: All three estrogens elicited cytotoxicity at high concentrations in both cell lines. They also inhibited cell proliferation, with E2 being the most effective. They all tended to increase micronuclei formation. CONCLUSION: Natural estrogens were no less toxic than a synthetic one.


Asunto(s)
Proliferación Celular , Estradiol , Flavanonas , Tartrazina , Humanos , Animales , Ratas , Estradiol/farmacología , Flavanonas/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Tartrazina/farmacología , Carcinoma Hepatocelular , Neoplasias Hepáticas/inducido químicamente , Células Hep G2 , Estrógenos/farmacología , Congéneres del Estradiol/farmacología , Fitoestrógenos/farmacología
2.
Int J Mol Sci ; 23(6)2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35328588

RESUMEN

8-prenylnaringenin (8-PN) is a prenylated flavonoid, occurring, in particular, in hop, but also in other plants. It has proven to be one of the most potent phytoestrogens in vitro known to date, and in the past 20 years, research has unveiled new effects triggered by it in biological systems. These findings have aroused the hopes, expectations, and enthusiasm of a "wonder-drug" for a host of human diseases. However, the majority of 8-PN effects require such high concentrations that they cannot be reached by normal dietary exposure, only pharmacologically; thus, adverse impacts may also emerge. Here, we provide a comprehensive and up-to-date review on this fascinating compound, with special reference to the range of beneficial and untoward health consequences that may ensue from exposure to it.


Asunto(s)
Flavanonas , Humulus , Flavonoides , Humanos , Fitoestrógenos
3.
Am J Physiol Regul Integr Comp Physiol ; 321(4): R603-R613, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34405712

RESUMEN

Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.


Asunto(s)
Proteínas de Peces/metabolismo , Carpa Dorada/metabolismo , Hipotálamo/metabolismo , Riñón/metabolismo , Nucleobindinas/metabolismo , Hipófisis/metabolismo , Animales , Células Cultivadas , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Proteínas de Peces/genética , Carpa Dorada/genética , Masculino , Nucleobindinas/genética , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Restricción Física
4.
Sci Rep ; 14(1): 3985, 2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368491

RESUMEN

Nucleobindin-derived peptides, nesfatin-1 [NESF-1] and nesfatin-1-like-peptide [NLP] have diverse roles in endocrine and metabolic regulation. While both peptides showed a stimulatory effect on the synthesis of proopiomelanocortin (POMC), the adrenocorticotropic hormone (ACTH) precursor in mouse corticotrophs, whether NESF-1 and NLP have any direct effect on glucocorticoid [GC] synthesis in the adrenal cortex remains unknown. The main aim of this study was to determine if NESF-1 and/or NLP act directly on adrenal cortex cells to regulate cortisol synthesis in vitro. Whether NLP injection affects stress-hormone gene expression in the adrenal gland and pituitary in vivo in mice was also assessed. In addition, cortisol synthetic pathway in Nucb1 knockout mice was studied. Human adrenal cortical [H295R] cells showed immunoreactivity for both NUCB1/NLP and NUCB2/NESF-1. NLP and NESF-1 decreased the abundance of steroidogenic enzyme mRNAs, and cortisol synthesis and release through the AC/PKA/CREB pathway in H295R cells. Similarly, intraperitoneal injection of NLP in mice decreased the expression of enzymes involved in glucocorticoid (GC) synthesis in the adrenal gland while increasing the expression of Pomc, Pcsk1 and Crhr1 in the pituitary. Moreover, the melanocortin 2 receptor (Mc2r) mRNA level was enhanced in the adrenal gland samples of NLP injected mice. However, the global genetic disruption in Nucb1 did not affect most steroidogenic enzyme mRNAs, and Pomc, Pcsk2 and Crhr1 mRNAs in mice adrenal gland and pituitary gland, respectively. Collectively, these data provide the first evidence for a direct inhibition of cortisol synthesis and secretion by NLP and NESF-1. NUCB peptides might still elicit a net stimulatory effect on GC synthesis and secretion through their positive effects on ACTH-MC2R pathway in the pituitary.


Asunto(s)
Corteza Suprarrenal , Hidrocortisona , Humanos , Ratones , Animales , Glucocorticoides , Proopiomelanocortina/metabolismo , Péptidos , Hormona Adrenocorticotrópica/farmacología , Corteza Suprarrenal/metabolismo
5.
Commun Biol ; 7(1): 623, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802487

RESUMEN

Nesfatin-1 (NESF-1) has been shown to modulate lipid metabolism. We have identified a nesfatin-1-like-peptide (NLP) processed from a related precursor nucleobindin 1 (NUCB1). Here we determined if NLP, like NESF-1, regulates lipid accumulation in vitro, and tested if the disruption of nucb1 gene affects hepatic lipid metabolism genes in mice. Hepatocytes (HepG2/C3A cells) express NLP and NESF-1 and both peptides significantly reduced lipogenic enzyme mRNAs and enhanced beta-oxidation enzyme mRNAs. Lipid contents in oleic acid induced HepG2/C3A cells were attenuated by NESF-1 and NLP. The inhibitory effect on cellular lipid content was blocked by compound C, an inhibitor of AMPK. The disruption of nucb1 gene affected lipid metabolism-related enzyme mRNAs, endogenous nucb2 mRNA and AMPK phosphorylation. The lipid-lowering effects identified here highlights the potential of nucleobindins and peptides processed from them to address lipid disorders, and its possible benefits in metabolic disease management.


Asunto(s)
Proteínas de Unión al Calcio , Proteínas de Unión al ADN , Hepatocitos , Metabolismo de los Lípidos , Proteínas del Tejido Nervioso , Nucleobindinas , Nucleobindinas/metabolismo , Nucleobindinas/genética , Animales , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ratones , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Células Hep G2 , Masculino , Ratones Endogámicos C57BL
6.
Biosensors (Basel) ; 13(3)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36979527

RESUMEN

Alleviating the increasingly critical environmental pollution problems entails the sensing of volatile organic compounds (VOCs) as a hazardous factor for human health wherein the development of gas sensor platforms offers an efficient strategy to detect such noxious gases. Nanomaterials, particularly carbon-based nanocomposites, are desired sensing compounds for gas detection owing to their unique properties, namely a facile and affordable synthesis process, high surface area, great selectivity, and possibility of working at room temperature. To achieve that objective, g-C3N4 (graphitic carbon nitride) was prepared from urea deploying simple heating. The ensuing porous nanosheets of g-C3N4 were utilized as a substrate for loading Au nanoparticles, which were synthesized by the laser ablation method. g-C3N4 presented a sensing sensitivity toward organic vapors, namely methanol, ethanol, and acetone vapor gases, which were significantly augmented in the presence of Au nanoparticles. Specifically, the as-prepared nanocomposite performed well with regard to the sensing of methanol vapor gas and offers a unique strategy and highly promising sensing compound for electronic and electrochemical applications.


Asunto(s)
Nanopartículas del Metal , Nanocompuestos , Humanos , Oro/química , Metanol , Nanopartículas del Metal/química , Nanocompuestos/química , Gases
7.
Mol Cell Endocrinol ; 536: 111401, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34302909

RESUMEN

Nucleobindin (NUCB)-derived peptides, nesfatin-1 (NES-1) and nesfatin-1-like peptide (NLP) have several physiological roles in vertebrates. While NES-1 is implicated in stress, whether NUCB1/NLP and NUCB2/NES-1 have any effect on proopiomelanocortin (POMC) remains unknown. The main aim of this study was to determine if NES-1 and/or NLP affect POMC synthesis in mouse corticotrophs. Immunocytochemistry was employed to target NUCB colocalization with POMC in immortalized mouse tumoral corticotrophs (AtT-20 cells). The ability of NES-1 and NLP to modulate POMC mRNA and protein in AtT-20 cells was assessed by qPCR and Western blot, respectively. Moreover, cell-signaling molecules mediating the effect of NES-1 and NLP on POMC synthesis in mouse tumoral corticotrophs were studied using pharmacological blockers. Mouse tumoral corticotrophs showed immunoreactivity for both NUCB1/NLP and NUCB2/NES-1. Both NES-1 and NLP exerted a stimulatory effect on POMC transcript abundance and protein expression in a dose- and time-dependent manner. This effect was comparable to corticotropin-releasing factor (CRF, positive control) stimulation of POMC. Incubation of mouse tumoral corticotrophs with NES-1 or NLP upregulated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). The stimulatory effect of these peptides on POMC transcript abundance and protein expression was blocked by the PKA inhibitor, H89, and an adenylate cyclase inhibitor, 2',3'-dideoxyadenosine (DDA). These pharmacological studies indicate that NES-1 and NLP act through the cAMP/PKA/CREB cellular pathway to stimulate POMC synthesis. Our results provide molecular evidence to support a stimulatory role for nucleobindin-derived peptides on POMC synthesis from corticotrophs. Collectively, this research indicates that corticotrophs produce NUCBs, and the encoded peptides NES-1 and NLP could elicit a direct action to stimulate the pituitary stress hormone. This stimulatory effect is mediated by an uncharacterized G protein-coupled receptor (GPCR) that utilizes the cAMP/PKA/CREB pathway.


Asunto(s)
Corticotrofos/citología , Nucleobindinas/metabolismo , Fragmentos de Péptidos/metabolismo , Proopiomelanocortina/metabolismo , Animales , Corticotrofos/efectos de los fármacos , Corticotrofos/metabolismo , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Didesoxiadenosina/farmacología , Regulación de la Expresión Génica , Isoquinolinas/farmacología , Ratones , Nucleobindinas/química , Nucleobindinas/genética , Proopiomelanocortina/genética , Transducción de Señal , Sulfonamidas/farmacología , Células Tumorales Cultivadas
8.
Environ Sci Pollut Res Int ; 28(22): 27988-27997, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33527240

RESUMEN

Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.


Asunto(s)
Genisteína , Tartrazina , Daño del ADN , Estrógenos , Genisteína/toxicidad , Humanos , Fitoestrógenos/toxicidad , Tartrazina/toxicidad
9.
Mol Cell Endocrinol ; 529: 111269, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33819522

RESUMEN

Prolactin (PRL), mainly synthesized and secreted by the lactotrophs and somatolactotrophs of the anterior pituitary, is a pleiotropic hormone that regulates lactation. In the last decade, nesfatin-1 (NESF) and NESF-like peptide (NLP), encoded in nucleobindin 1 and 2 (NUCB1 and NUCB2), respectively, were characterized as metabolic factors with a potential role in the control of pituitary hormones. We hypothesized that NUCBs and their encoded peptides (NESF and NLP) suppress PRL transcription in the pituitary. The main objective of this research was to determine whether exogenous NESF and NLP, and/or endogenous NUCB1 and NUCB2 regulate the expression of prl and preb mRNAs. Using immortalized rat somatolactotrophs (GH3 cells), dose-response studies were performed to test whether NESF and NLP affect prl and preb. Moreover, the ability of these peptides to modulate the effects of the PRL stimulator thyrotropin releasing hormone (TRH) was studied. Besides, the effects of siRNA-mediated knockdown of endogenous NUCBs on prl and preb mRNAs were determined. NESF and NLP reduced the transcription of prl and preb in GH3 cells. Both NESF and NLP also prevented the stimulatory effects of TRH prl and preb expression. The knockdown of endogenous NUCB1 attenuates both basal prl and TRH-induced expression of prl and preb, while the silencing of NUCBs did not affect the actions of exogenous NESF or NLP. Overall, this work reveals that NUCBs and encoded-peptides are novel regulators of PRL. Future research should test whether the effects observed here in GH3 cells are preserved both in vivo and at the post-transcriptional level.


Asunto(s)
Proteínas de Unión al ADN/genética , Factores de Intercambio de Guanina Nucleótido/genética , Lactotrofos/efectos de los fármacos , Nucleobindinas/farmacología , Péptidos/farmacología , Prolactina/genética , Somatotrofos/efectos de los fármacos , Factores de Transcripción/genética , Animales , Línea Celular Transformada , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Factores de Intercambio de Guanina Nucleótido/antagonistas & inhibidores , Factores de Intercambio de Guanina Nucleótido/metabolismo , Lactotrofos/citología , Lactotrofos/metabolismo , Nucleobindinas/antagonistas & inhibidores , Nucleobindinas/genética , Nucleobindinas/metabolismo , Prolactina/antagonistas & inhibidores , Prolactina/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Transducción de Señal , Somatotrofos/citología , Somatotrofos/metabolismo , Hormona Liberadora de Tirotropina/genética , Hormona Liberadora de Tirotropina/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo
10.
Int J Biol Macromol ; 182: 1056-1090, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33872617

RESUMEN

Over the course of a few decades, the concern of environmental damages of fossil fuels, an increase in CO2 emission and a decrease of hydrogen have been growing more and more. Accordingly, hydrogen production is a crucial issue nowadays. Different polymers are applied to attain the purpose. Among all polymers, biodegradables polymers are the best choices to develop the main aim. Polysaccharides and proteins are biodegradable polymers with unique places and advantages with regards to their ecofriendly properties. There are different techniques to apply and achieve the foremost purpose. It is worthwhile to mention that green and facile methods are always attracting attention in different aspects and fields. The three non-polluting and economical techniques, that is, electrochemical hydrogen evolution reaction (HER), photocatalytic technique, and hydrolysis of hydrides, are reviewed in this paper. This review helps researchers, who are environment supporters, to evaluate and choose the most ecological biopolymers and processes in their work.


Asunto(s)
Polímeros/química , Biopolímeros/química , Catálisis , Electroquímica , Hidrógeno/química , Hidrólisis , Polisacáridos/química
11.
Int J Biol Macromol ; 164: 3012-3024, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32835803

RESUMEN

This paper reports a novel nanocomposite catalyst comprised of graphitic carbon nitride (g-C3N4), chitosan and gold (Au) nanoparticles, which has been prepared through a facile, clean and low cost method. Graphitic carbon nitride has been fabricated by pyrolysis of urea. Laser ablation in liquid (LAL) was employed in the green synthesis of Au NPs. The g-C3N4/chitosan/Au nanocomposite (denoted as CN/CS/Au) were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy dispersive X-ray spectrometry (EDS), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analyses. Chitosan biopolymer and a small amount of Au NPs were added to g-C3N4 to modify and improve the catalytic activity of g-C3N4. The activity of the hydrogen evolution reaction (HER) has been investigated using CN/CS/Au nanocomposite coated on a stainless steel mesh by electrochemical method. The amounts of hydrogen stored were calculated from cyclic voltammetry (CV) results. The results confirmed that chitosan and Au NPs were effective on the HER behavior of g-C3N4 and the nanocomposite had a good HER activity and stability.


Asunto(s)
Quitosano/química , Oro/química , Grafito/química , Hidrógeno/química , Compuestos de Nitrógeno/química , Estabilidad de Medicamentos , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanocompuestos , Espectroscopía de Fotoelectrones , Espectroscopía Infrarroja por Transformada de Fourier , Acero Inoxidable , Difracción de Rayos X
12.
Toxicol In Vitro ; 52: 178-188, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29908305

RESUMEN

The mediator of dioxin toxicity, aryl hydrocarbon receptor (AHR), has also important physiological functions. Selective AHR modulators (SAHRMs) share some effects of dioxins, except for their marked toxicity. We recently characterised toxicologically two novel SAHRMs, prodrugs IMA-08401 and IMA-07101 in rats, demonstrating that they are far less deleterious than the most toxic AHR-agonist, TCDD. Here, we analysed the in vitro toxicity and in silico AHR binding of the respective active, deacetylated metabolites, IMA-06201 (N-ethyl-N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-06504 (N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). In H4IIE rat hepatoma cells, IMA-06201 and IMA-06504 induced CYP1A1 with comparable potencies and efficacies to those of TCDD. They had little effect on cell viability as assessed by LDH leakage and MTT reduction assays, and were not mutagenic in the Ames test, but IMA-06504 elicited a maximally 2.7-fold increase in micronuclei. Molecular docking simulations showed that similar to TCDD, they occupy the central region of AHR ligand binding cavity. Hence, while showing low to negligible in vitro toxicity, these novel SAHRMs bind to the AHR qualitatively in a similar fashion to TCDD, and appear comparably powerful AHR agonists. Combined with our earlier results demonstrating that they seem considerably less toxic in vivo than TCDD, these compounds are thus highly interesting new SAHRMs.


Asunto(s)
Quinolinas/farmacología , Quinolinas/toxicidad , Receptores de Hidrocarburo de Aril/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocromo P-450 CYP1A1/metabolismo , Simulación del Acoplamiento Molecular , Pruebas de Mutagenicidad , Ratas
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