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1.
J Biol Chem ; 299(11): 105310, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37778728

RESUMO

T-cell receptor stimulation triggers cytosolic Ca2+ signaling by inositol-1,4,5-trisphosphate (IP3)-mediated Ca2+ release from the endoplasmic reticulum (ER) and Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels gated by ER-located stromal-interacting molecules (STIM1/2). Physiologically, cytosolic Ca2+ signaling manifests as regenerative Ca2+ oscillations, which are critical for nuclear factor of activated T-cells-mediated transcription. In most cells, Ca2+ oscillations are thought to originate from IP3 receptor-mediated Ca2+ release, with CRAC channels indirectly sustaining them through ER refilling. Here, experimental and computational evidence support a multiple-oscillator mechanism in Jurkat T-cells whereby both IP3 receptor and CRAC channel activities oscillate and directly fuel antigen-evoked Ca2+ oscillations, with the CRAC channel being the major contributor. KO of either STIM1 or STIM2 significantly reduces CRAC channel activity. As such, STIM1 and STIM2 synergize for optimal Ca2+ oscillations and activation of nuclear factor of activated T-cells 1 and are essential for ER refilling. The loss of both STIM proteins abrogates CRAC channel activity, drastically reduces ER Ca2+ content, severely hampers cell proliferation and enhances cell death. These results clarify the mechanism and the contribution of STIM proteins to Ca2+ oscillations in T-cells.


Assuntos
Canais de Cálcio Ativados pela Liberação de Cálcio , Sinalização do Cálcio , Humanos , Cálcio/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/genética , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Sinalização do Cálcio/genética , Células Jurkat , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Molécula 2 de Interação Estromal/genética , Molécula 2 de Interação Estromal/metabolismo , Técnicas de Inativação de Genes , Modelos Biológicos , Isoformas de Proteínas , Transporte Proteico/genética , Proliferação de Células/genética , Sobrevivência Celular/genética
2.
Trop Anim Health Prod ; 56(4): 145, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676831

RESUMO

In order to analyze the environmental performance of Smallholder Dairy Farms (SHDFs) located in the State of Mexico, a Life Cycle Analysis (LCA) was carried out using two methodological approaches (A1 and A2) to estimate and interpret environmental impacts. A1 consisted in obtaining the average inputs and outputs of 15 SHDFs to generate a representative farm life cycle inventory, while A2 included an individual environmental impact analysis per SHDF to obtain average values of the contributions per analyzed midpoint impact category. The feed production subsystem generated the highest contributions to environmental impacts per liter of raw milk produced. Estimated emissions based on A2 approach, resulted in higher environmental impacts compared to results obtained with A1. The estimated values for the midpoint impact categories obtained with A2: Climate change, Fossil depletion, Terrestrial acidification, and Agricultural land occupation, were 8.73%, 30.77%, 100%, and 20.49% higher compared to A1 approach, respectively. While A2 provides more accurate results, it requires more time and resources compared to the integration of a panel of representative dairy farms.


Assuntos
Indústria de Laticínios , Meio Ambiente , México , Indústria de Laticínios/métodos , Animais , Bovinos , Leite/química , Mudança Climática
3.
J Phycol ; 55(2): 297-313, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30570145

RESUMO

A recent molecular taxonomic study along the Chilean coast (18° S-53° S) described 18 candidate species of bladed Bangiales of which only two were formally described. Few studies focused on local genetic and morphological diversity of bladed Bangiales and attempted to determine their intertidal distribution in contrasting habitats, and none were performed in Chile. To delimit intertidal distributions of genetic species, 66 samples of bladed Bangiales were collected at Maitencillo (32° S) in four zones: a rocky platform, a rocky wall, and two boulders zones surrounded by sandy and rocky bottoms, respectively. These samples were identified based on sequences of the mitochondrial COI and chloroplast rbcL markers. We also collected 87 specimens for morphological characterization of the most common species, rapidly assessing their putative species identity using newly developed species-diagnostic (PCR-RFLP) markers. Eight microscopic and two macroscopic morphological traits were measured. We described and named three of four species that predominate in Maitencillo (including Pyropia orbicularis): Pyropia variabilis Zapata, Meynard, Ramírez, Contreras-Porcia, sp. nov., Porphyra luchea Meynard, Ramírez, Contreras-Porcia sp. nov., and Porphyra longissima Meynard, Ramírez, Contreras-Porcia, sp. nov. With the exception of Po. longissima restricted to boulders surrounded by sandy bottom, and a morphotype of Py. variabilis restricted to rocky walls, the other species/morphotypes have overlapping intertidal distributions. Except for Po. longissima, which is clearly differentiated morphologically (longest and thinnest blades), we conclude that morphology is not sufficient to differentiate bladed Bangiales. Our findings underscore the importance of refining our knowledge of intrinsic and environmental determinants on the distribution of bladed Bangiales.


Assuntos
Porphyra , Rodófitas , Chile , Filogenia
4.
Planta ; 245(6): 1149-1164, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28289905

RESUMO

MAIN CONCLUSION: The transcriptional modulation of desiccation tolerance factors in P. orbicularis explains its successful recuperation after water deficit. Differential responses to air exposure clarify seaweed distribution along intertidal rocky zones. Desiccation-tolerant seaweed species, such as Pyropia orbicularis, can tolerate near 96% water loss during air exposure. To understand the phenotypic plasticity of P. orbicularis to desiccation, several tolerance factors were assessed by RT-qPCR, Western-blot analysis, and enzymatic assays during the natural desiccation-rehydration cycle. Comparative enzymatic analyses were used to evidence differential responses between P. orbicularis and desiccation-sensitive species. The results showed that during desiccation, the relative mRNA levels of genes associated with basal metabolism [trehalose phosphate synthase (tps) and pyruvate dehydrogenase (pdh)] were overexpressed in P. orbicularis. Transcript levels related to antioxidant metabolism [peroxiredoxin (prx); thioredoxin (trx); catalase (cat); lipoxygenase (lox); ferredoxin (fnr); glutathione S-transferase (gst)], cellular detoxification [ABC transporter (abc) and ubiquitin (ubq)], and signal transduction [calmodulin (cam)] increased approximately 15- to 20-fold, with the majority returning to basal levels during the final hours of rehydration. In contrast, actin (act) and transcription factor 1 (tf1) transcripts were down-regulated. ABC transporter protein levels increased in P. orbicularis during desiccation, whereas PRX transcripts decreased. The antioxidant enzymes showed higher specific activity in P. orbicularis under desiccation, and sensitive species exhibited enzymatic inactivation and scarce ABC and PRX protein detection following prolonged desiccation. In conclusion, the reported findings contribute towards understanding the ecological distribution of intertidal seaweeds at the molecular and functional levels.


Assuntos
Dessecação , Alga Marinha/metabolismo , Western Blotting , Catalase/genética , Catalase/metabolismo , Ferredoxinas/genética , Ferredoxinas/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Lipoxigenase/genética , Lipoxigenase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Alga Marinha/genética , Transdução de Sinais , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
5.
Trop Anim Health Prod ; 47(2): 331-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25471363

RESUMO

In Mexico, small-scale dairy systems (SSDS) represent over 78 % of dairy farms and contribute with 37 % of national milk production; however, they face high feeding costs. The objective of this study was to assess the performance of SSDS during the dry season in terms of milk yields, milk composition and feeding costs under traditional feeding strategies, to identify areas of opportunity for improving their profitability. The information was collected from 22 SSDS every month during dry season. Feeds were classified in quality forages (QF), supplements (SU) and straws (ST). Two factors were identified: factor 1-a positive relationship among QF, SU, milk yield and ration cost and factor 2-represented straw usage. Four feeding strategies were identified: (1) low-cost feeding strategy; (2) home-grown feeding strategy; (3) high-cost feeding strategy; and (4) straw-based feeding strategy. There were differences (P < 0.001) among feeding strategies for QF, SU, ST, total dry matter offered (TDMO), ration cost (RC), external inputs, home-grown inputs and milk yield. There were no significant (P > 0.05) differences among feeding strategies for fat and protein contents in milk. It is concluded that to improve performance and profitability and enhance sustainability in SSDS, farmers should base feeding strategies on home-grown quality forages, as it was the case in group 2 which showed lower feeding cost and better milk yield. It is also recommended to increase the inclusion of quality forages like grazing pastures and maize silages during the dry season and to avoid the inclusion of straws.


Assuntos
Ração Animal , Criação de Animais Domésticos/economia , Indústria de Laticínios/economia , Leite/economia , Animais , Bovinos , Secas , Feminino , México , Estações do Ano
6.
Trop Anim Health Prod ; 46(1): 235-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24097246

RESUMO

The objective of this work was to determine the effect of family labour on the profitability and competitiveness of small-scale dairy farms in the highlands of Central Mexico. Economic data from 37 farms were analysed from a stratified statistical sampling with a Neyman assignment. Three strata were defined taking herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements, Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The policy analysis matrix was used as the method to determine profitability and competitiveness. The coefficient of private profitability (CPP) when the economic cost of family labour is included in the cost structure was 8.0 %, 31.0 % and 46.0 %. When the economic cost of family labour is not included, CPP increase to 47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and 3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and 0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is not included. It is concluded that family labour is a crucial factor in the profitability and competitiveness of small-scale dairy production.


Assuntos
Indústria de Laticínios/economia , Família , Leite/economia , Animais , Bovinos , Indústria de Laticínios/métodos , Feminino , Humanos , México
7.
Sci Total Environ ; 946: 174240, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38925383

RESUMO

Medium-scale pig production systems, which make up 30 % of Mexico's pig farms, face two key obstacles impacting their economic and financial performance. The first is the absence of a sales plan based on pigs' weight, which negatively affects both profitability and resource management. The second obstacle is inadequate waste management, which hampers efforts to mitigate environmental impacts generated by pig farms. Based on this criterion, this study aims to determine technical and economic optimum levels of a medium-scale pig farm and evaluate its associated environmental impacts. Based on the last farm sale weight (116.3 kg - base scenario), technical and economic optimum levels were estimated using a production function, resulting in a technical optimum of 155 kg and an economic optimum of 127 kg. An environmental assessment of the pig fattening process was carried out following the principles of the Life Cycle Analysis methodological framework. Using a cradle-to-farm gate perspective, and establishing 1 kg of live-weight pig as the functional unit. The results indicated that production at maximum weight level (155 kg), increased environmental impacts by 60 % to 75 % compared to the base scenario. In contrast, at the maximum economic benefit level (127 kg), environmental impacts increased by 5 % to 10 %. Feed production represented the largest contribution (over 74 %) in six impact categories. The results provide valuable information for medium-scale pig farms to mitigate the environmental burdens associated with the optimal production weight and to direct efforts towards achieving future economic and environmental efficiency.


Assuntos
Criação de Animais Domésticos , Meio Ambiente , Animais , México , Criação de Animais Domésticos/métodos , Suínos , Fazendas
8.
PLoS One ; 19(5): e0298897, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722980

RESUMO

To estimate the economic and financial viability of a pig farm in central sub-tropical Mexico within a 5-year planning horizon, a Monte Carlo simulation model was utilized. Net returns were projected using simulated values for the distribution of input and product processes, establishing 2021 as base scenario. A stochastic modelling approach was employed to determine the economic and financial outlook. The findings reveal a panorama of economic and financial viability. Net income increased by 555%, return on assets rose from 3.36% in 2022 to 11.34% in 2026, and the probability of decapitalization dropped from 58% to 13%, respectively in the aforesaid periods. Similarly, the probability of obtaining negative net income decreased from 40% in 2022 to 18% in 2026. The technological, productive, and economic management of the production unit allowed for a favorable scenario within the planning horizon. There is a growing interest in predicting the economic sectors worth investing in and supporting, considering their economic and development performance. This research offers both methodological and scientific evidence to demonstrate the feasibility of establishing a planning schedule and validating the suitability of the pork sector for public investment and support.


Assuntos
Fazendas , México , Animais , Suínos , Fazendas/economia , Modelos Econômicos , Criação de Animais Domésticos/economia , Método de Monte Carlo , Estudos Prospectivos , Renda
9.
Theriogenology ; 207: 49-60, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37269596

RESUMO

The aim of this work was to determine endometrial mRNA expression and uterine protein localization of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 during the estrous cycle and peri-implantation period in sows. Uterine tissues were collected from pregnant sows on days 12, 14, 16, and 18 after artificial insemination and from non-pregnant animals on days 2 and 12 of the estrous cycle (day 0 = day of estrus). Using immunohistochemistry, a positive signal for VEGF and its receptor VEGFR2 was found in uterine luminal epithelial cells, endometrial glands, stroma, blood vessels, and myometrium. A VEGFR1 signal was only found in endometrial and myometrial blood vessels and stroma. By day 18 of gestation, the mRNA expression levels of VEGF, VEGFR1, and VEGFR2 were higher than those observed on days 2 and 12 of the estrous cycle and on days 12, 14, and 16 of gestation. Then, a primary culture of sow endometrial epithelial cells was established to define the potential of the selective inhibition of VEGFR2 after treatment with inhibitor SU5416 and determine its effects on the expression pattern of the VEGF system. The endometrial epithelial cells treated with SU5416 showed a dose-dependent decrease in VEGFR1 and VEGFR2 mRNA expression. The present study provides additional evidence on the importance of the VEGF system during peri-implantation, as well as on the specific inhibitory activity of SU5416 in epithelial cells, which, as demonstrated, express the protein and mRNA of VEGF and its receptors VEGFR1 and VEGFR2.


Assuntos
Inibidores da Angiogênese , Fator A de Crescimento do Endotélio Vascular , Animais , Suínos , Feminino , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/metabolismo , Útero/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo
10.
Handb Exp Pharmacol ; (203): 105-26, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21484569

RESUMO

Recently, the idea has been developed to lower blood glucose blood glucose levels in diabetes by inhibiting sugar reabsorption sugar reabsorption in the kidney kidney . The main target is thereby the early proximal tubule proximal tubule where secondary active transport secondary active transport of the sugar is mediated by the sodium-D: -glucose D-glucose cotransporter SGLT2 SGLT2 . A model substance for the inhibitors inhibitors is the O-glucoside O-glucoside phlorizin phlorizin which inhibits transport transport competitively. Its binding to the transporter involves at least two different domains: an aglucone binding aglucone binding site at the transporter surface, involving extramembranous loops extramembraneous loops , and the sugar binding sugar binding /translocation site buried in a hydrophilic pocket of the transporter. The properties of these binding sites differ between SGLT2 and SGLT1 SGLT1 , which mediates sugar absorption sugar absorption in the intestine intestine . Various O-, C-, N- and S-glucosides have been synthesized with high affinity affinity and high specificity specificity for SGLT2 SGLT2 . Some of these glucosides are in clinical trials clinical trials and have been proven to successfully increase urinary glucose excretion urinary glucose excretion and to decrease blood sugar blood sugar levels without the danger of hypoglycaemia hypoglycaemia during fasting fasting in type 2 diabetes type 2 diabetes .


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Animais , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/síntese química , Florizina/análogos & derivados , Florizina/síntese química , Florizina/farmacologia , Relação Estrutura-Atividade
11.
Environ Sci Pollut Res Int ; 28(14): 18300-18307, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33704637

RESUMO

Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) are persistent toxicants in coastal environments. Notably, in comparison to individual metal toxicity, knowledge about the effects of HMs and PAHs mixtures on kelps remains scarce. Accordingly, we performed in vitro experiments to determine the individual and combined effects of Cu, Cd, and PAHs on spore release, settlement, and germination on Macrocystis pyrifera and Lessonia spicata, two key-habitat forming kelp species of the coast of the Valparaíso Region in Chile. This region concentrates highly polluting industries, mainly due to unrestrained mining and fossil-fuel energy production. Single Cu, Cd, and PAHs treatments included concentrations in the ranges 5-200, 0.125-2000, and 0.05-100 µg/L, respectively, and a toxic-free treatment. Cu, Cd, and PAHs concentrations causing 20-50% (IC20, IC50) arrested spore release, settlement, and germination were determined, and the results shown in both species that single Cu, Cd, and PAHs IC20 values were generally lower on spore release than on spore settlement and germination, probably due to the absence of a cell wall in spores compared to later stages. Binary equitoxic IC20s mixture treatments changed from an antagonistic response to another with a greater inhibitory effect on spore release, from hour 1 to 7, whereas in IC50 treatments, the response was always antagonistic. The tertiary IC20 mixture of Cu+Cd+PAHs produced generally an antagonistic effect. Remarkably, all IC20 equitoxic mixture treatments showed a synergistic response on spore settlement in both kelps, suggesting that these toxicants are extremely harmful to kelp population persistence near highly polluted sites.


Assuntos
Kelp , Metais Pesados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Cádmio , Chile , Cobre , Ecossistema
12.
Toxics ; 9(8)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34437508

RESUMO

The study of pollution effects in the marine environment has become important in recent decades, and the exposure to simultaneous pollutants has become especially relevant. Indeed, the study of key organisms, such as ecosystem engineers, can show a broader view of the effects of pollutants. In this context, we evaluate in situ the effects of a short (7-day) pollution pulse of combined solutions of heavy metals and polycyclic aromatic hydrocarbons (PAHs) (Cu + PAHs, Cd + PAHs, Cu + Cd, and Cu + Cd + PAHs) on the development and morphological features of Macrocystis pyrifera sporophytes over a period of 90 days. Additionally, we determined the effects on the community structure associated with this kelp. This study evidenced a smaller number of blades and a decreased size of blades and holdfasts, as well as the death of individuals exposed to a secondary mix of metals (Cu + Cd) and a tertiary mix of pollutants (Cu + Cd + PAHs). Regarding the effects on the accompanying fauna, low richness and diversity were registered. M. pyrifera grazers, according to the mixture of pollutants, were either absent or diminished. These results show that the pulse of contamination in the early stages of M. pyrifera negatively affects its development and morphometry, as well as its role as an ecosystem engineer, due to a negative alteration in the species composition.

13.
Nutrients ; 13(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071972

RESUMO

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and ß-carotene. Accordingly, Gracilex® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.


Assuntos
Gracilaria/química , Resistência à Insulina/fisiologia , Obesidade/metabolismo , PPAR gama/metabolismo , Extratos Vegetais , Animais , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/farmacologia , Caenorhabditis elegans , Modelos Animais de Doenças , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia
14.
Acta Histochem ; 123(5): 151741, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34197981

RESUMO

The Vietnamese pot-bellied pig is a breed with high investigation potential. However, at the reproductive level, its testicular characteristics are still unknown, as well as the different stages of its development. Therefore, the objective of this work is to describe the postnatal testicular development of Vietnamese pot-bellied pigs. In this study, we used pigs grouped into the neonatal stage, animals at zero weeks; prepubertal stage, animals at three and eight weeks; pubertal stage, animals at twelve and sixteen weeks; and postpubertal stage animals at twenty, twenty-four, twenty-eight and thirty-two weeks of age. The neonatal stage is characterized by gonocytes at different migration phases. In the prepubertal stage, gonocytes were differentiated into spermatogonia at 3 weeks of age, and the first spermatocytes were observed at 7 weeks of age. Puberty was determined to start at 12 weeks because seminiferous tubules are found with complete spermatogenesis and the highest peaks in positive cell counting of androgen receptors (AR) and proliferating cell nuclear antigen (PCNA) factor that later decreased and further stabilized in the following weeks. In the postpubertal stage, an increase in seminiferous tubule areas was observed. The number of apoptotic cells ranged from low to null at all ages. Testosterone (T) and gonadotropin levels had two important peaks at 3 and 24 weeks. The seminiferous epithelium cycle was found to have 11 stages according to acrosome development. These characteristics of Vietnamese pot-bellied pig testes, which are different from rat testes and more similar to human testicles, make them a viable model to study human male reproductive biology. The postnatal testicular development of pot-bellied pigs is different from the postnatal testicular development of other breeds. Therefore, due to this difference in size and easy manipulation, the Vietnamese pig is an alternative for investigation compared to other pig breeds.


Assuntos
Escroto/crescimento & desenvolvimento , Epitélio Seminífero/crescimento & desenvolvimento , Espermatogônias/crescimento & desenvolvimento , Testículo/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Proliferação de Células , Humanos , Masculino , Modelos Animais , Antígeno Nuclear de Célula em Proliferação/metabolismo , Receptores Androgênicos , Túbulos Seminíferos/crescimento & desenvolvimento , Espermatogênese/fisiologia , Suínos , Fatores de Tempo
15.
J Cell Biochem ; 109(6): 1109-17, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20069550

RESUMO

The sodium-dependent glucose co-transporter (SGLT1) is regulated by protein kinases. The aim of the present study was to examine the role of protein kinase C (PKC) in the regulation of rabbit (rb) SGLT1 activity as determined by alpha-methyl-D-glucopyranoside (AMG) uptake and to identify the cellular mechanisms involved in this process. For this purpose Chinese hamster ovary cells expressing rbSGLT1 (CHO-G6D3) were treated with PKC activators and inhibitors. PKC activators did not exert any effect on AMG uptake, as corroborated by mutation of the putative phosphorylation sites of PKC. In contrast, the PKC inhibitor bisindolylmaleimide I (BIM) increased AMG uptake. This effect was associated with translocation of rbSGLT1 from the intracellular pool to the plasma membrane demonstrated by pre-treatment of G6D3 cells with cytochalasin D that abolished the effect of BIM. In addition, intracellular signaling pathways (p38/MAPK, ERK/MAPK, JNK/MAPK, and PI3K/Akt/mTOR) were associated with PKC-regulated AMG uptake. Moreover, rbSGLT1 mRNA level was higher in BIM-treated cells than in untreated, control cells. This effect was completely abolished by actinomycin D treatment. The present study demonstrates that PKC regulates rbSGLT1 activity via a complex intracellular mechanism that involves sorting and transcriptional regulation of rbSGLT1. The study findings suggest the involvement of two complementary opposite mechanism of action, in which the balance between two antagonistic effects, namely stimulation and inhibition of the transporter, regulates the activity of rbSGLT1 by PKC.


Assuntos
Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Western Blotting , Células CHO , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Imuno-Histoquímica , Indóis/farmacologia , Maleimidas/farmacologia , Metilglucosídeos/metabolismo , Mutagênese Sítio-Dirigida , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/genética , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
J Physiol Biochem ; 66(2): 105-15, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20428992

RESUMO

The present study explored whether calcitriol plays a role in the regulation of sodium-dependent glucose transporter protein 1 (SGLT1) activity. For this purpose, alpha-methyl glucoside (AMG) uptake in stable transfected Chinese hamster ovary (CHO-G6D3) cells expressing rabbit SGLT1 (rbSGLT1) was used. The involvement of second messengers, intracellular signaling pathways, and pro-inflammatory cytokines were examined using specific inhibitors before incubation with calcitriol for 15 min. The present study demonstrated the involvement of second messengers produced by phospholipase A(2), phospholipase C, calmodulin, diacylglycerol kinase, and phosphoinositide 3 kinase on calcitriol-regulated AMG uptake. Pretreatment with inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway increased calcitriol-induced AMG uptake. In contrast, inhibition of the phosphoinositide 3-kinase PI3K/Akt/mTOR signaling pathway decreased the effect of calcitriol on AMG uptake. These findings suggest that calcitriol regulates rbSGLT1 activity through a rapid, extranuclear initiated mechanism of action stimulated by MAPK and inhibited by PI3K/Akt/mTOR. Another important finding was the effect of pro-inflammatory cytokines on calcitriol-induced AMG uptake. Interleukin-6 increased while tumor necrosis factor-alpha decreased calcitriol-induced AMG uptake. In conclusion, the present study demonstrates the involvement of calcitriol in the regulation of rbSGLT1 activity. This is due to the activation of intracellular signaling pathways triggered by second messenger molecules and cytokines after a short time (15 min) exposure to calcitriol.


Assuntos
Calcitriol/farmacologia , Sistemas do Segundo Mensageiro/fisiologia , Transportador 1 de Glucose-Sódio/metabolismo , Animais , Células CHO , Cricetinae , Cricetulus , Interleucina-6/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metilglucosídeos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR , Fator de Necrose Tumoral alfa/metabolismo
17.
J Cell Biochem ; 106(3): 444-52, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19115253

RESUMO

In Chinese hamster ovary cells expressing rabbit sodium-dependent glucose transporter (rbSGLT1) protein kinase A (PKA) activators (forskolin and 8-Br-cAMP) stimulated alpha-methyl D-glucopyranoside uptake. Kinetic analysis revealed an increase in both V(max) and affinity of the transport. Immunohistochemistry and biotinylation experiments showed that this stimulation was accompanied by an increased amount of SGLT1 localized into the plasma membrane, which explains the higher V(max) of the transport. Cytochalasin D only partly attenuated the effect of forskolin as did deletion of the PKA phosphorylation site of SGLT1 in transient transfection studies. Experiments using an anti-phosphopeptide antibody revealed that forskolin also increased the extent of phosphorylation of SGLT1 in the membrane fraction. These results suggested that regulation of SGLT1 mediated glucose transport involves an additional direct effect on SGLT1 by phosphorylation. To evaluate this assumption further, phosphorylation studies of recombinant human SGLT1 (hSGLT1) in vitro were performed. In the presence of the catalytic subunit PKA and [(32)P] ATP 1.05 mol of phosphate were incorporated/mol of hSGLT1. Additionally, phosphorylated hSGLT1 demonstrated a reduction in tryptophan fluorescence intensity and a higher quenching by the hydrophilic Trp quencher acrylamide, particularly in the presence of D-glucose. These results indicate that PKA-mediated phosphorylation of SGLT1 changes the conformation of the empty carrier and the glucose carrier complex, probably causing the increase in transport affinity. Thus, PKA-mediated phosphorylation of the transporter represents a further mechanism in the regulation of SGLT1-mediated glucose transport in epithelial cells, in addition to a change in surface membrane expression.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Transportador 1 de Glucose-Sódio/química , Transportador 1 de Glucose-Sódio/metabolismo , Animais , Células CHO , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Ativação Enzimática , Humanos , Metilglucosídeos/metabolismo , Fosforilação , Coelhos , Transportador 1 de Glucose-Sódio/genética , Especificidade por Substrato
18.
Rev. ADM ; 80(5): 267-273, sept.-oct. 2023.
Artigo em Espanhol | LILACS | ID: biblio-1531449

RESUMO

El propósito del presente trabajo está orientado a generar una reflexión entre el gremio odontológico profesional y los estudiantes de las licenciaturas en Odontología respecto a la contaminación global que estamos generando y a la crítica situación del planeta, así como sus consecuencias ambientales y climatológicas, sobre lo importante que es educar bajo la perspectiva de una Odontología Verde y Sostenible a través de la ambientalización curricular en las escuelas y facultades de Odontología para generar un tipo de cultura y conciencia proambiental. De igual forma para señalar lo sencillo que es ambientalizar agradable y relajantemente nuestro entorno educativo y laboral, así como realizar algunas prácticas odontológicas ecológicas y ambientales en la práctica privada que cuestan poco o nada y que, por el contrario, el gran efecto positivo que éstas tendrán en el medio ambiente y la reducción de los niveles de contaminación actuales. Si realmente logramos generar una nueva cultura y conciencia que se preocupe por el medio ambiente en el campo de la Odontología, los resultados para todos se verán reflejados en un mejor ambiente social, educativo de trabajo y de salud (AU)


The purpose of this work is aimed at generating a reflection between the professional dental guild and the students of the Bachelor's Degrees in Dentistry regarding the global pollution that we are generating and the critical situation of the planet and its environmental and climatological consequences, on how important it is educate under the perspective of a Green and Sustainable Dentistry through the greening of the curriculum in the Schools and Faculties of Dentistry to generate a type of culture and pro-environmental awareness. Likewise, point out how simple it is to pleasantly and relaxingly green our educational and work environment, as well as perform some ecological and environment, as well perform some ecological and environment, dental practices in private practice that cost little or nothing and that, on the contrary, the great positive effect that these will have on the environment and the reduction of current pollution levels. If we truly manage to generate a new culture and awareness that cares about the environment in the field of Dentistry, the results for all will be reflected in a better social, educational, work and health environment (AU)


Assuntos
Odontologia/tendências , Meio Ambiente , Poluição Ambiental/prevenção & controle , Conscientização , Mudança Climática , Equipamentos Odontológicos/tendências , Indicadores de Desenvolvimento Sustentável
19.
Enferm. nefrol ; 26(3): 241-249, jul.-sep. 2023. tab, graf
Artigo em Inglês | IBECS (Espanha) | ID: ibc-226212

RESUMO

Introducción: Esta constatado un aumento de peso postrasplante renal, entre otros factores, por una reducción de la actividad física en los primeros meses, aumento del apetito y toma de inmunosupresores y corticoides. Objetivo: Conocer la ganancia de peso postrasplante. Determinar relación entre ganancia de peso y comorbilidades. Evaluar la modificación de la composición corporal. Material y Método: Estudio prospectivo, septiembre 2020-abril 2023. Se realizaron mediciones de peso a los 0, 3, 6, 12 meses. Resultados: Se analizaron 92 pacientes, 68,5% varones, edad 58±18,5 años. Peso pretrasplante 72,5 (±5,8), a los 12 meses: 75,10 (±15,7) kg. Se encontraron diferencias entre primero y trasplantes previos (p=0,020). En el análisis de las varianzas de medidas repetidas de peso (p=0,022), las diferencias se mostraron entre el mes 0 y el tercero, el mes 0 y el año y, entre el tercer mes y el año.En la masa muscular (p<0,001), se vieron al comparar el mes 0 con 3º, con 6º y con 12 meses. La masa grasa al comparar 3er mes con 12 meses y la grasa visceral (p=0,032), al comparar 3er mes con 6º y con 12 meses. Conclusión: Tras el trasplante renal se produce un aumento de peso, especialmente a partir del 6º mes, situándose en un 5% al año. La masa muscular aumenta en mayor medida que la masa grasa. Las personas trasplantadas de donante vivo, trasplante previos, con hipertensión y/o enfermedad cardiovascular tienen mayor ganancia de peso. (AU)


Introduction: Weight gain after kidney transplant has been documented, among other factors, due to reduced physical activity in the early months, increased appetite, and the use of immunosuppressants and corticosteroids. Objetives: To understand post-transplant weight gain. Indeed, to determine the relationship between weight gain and comorbidities, as well as, to evaluate changes in body composition. Material and Method: Prospective study, September 2020 to April 2023. Weight measurements were taken at 0, 3, 6, and 12 months. Results: Ninety-two patients were analyzed, 68.5% male, with an average age of 58±18.5 years. Pre-transplant weight was 72.5 (±5.8) kg, and at 12 months, it was 75.10 (±15.7) kg. Differences were found between first-time and repeat transplants (p=0.020). In the analysis of repeated measures of weight (p=0.022), differences were observed between month 0 and the third month, month 0 and one year, and between the third month and one year.In muscle mass (p<0.001), differences were seen when comparing month 0 with the third, sixth, and twelfth months. Fat mass differed when comparing the third month with the twelfth month, and visceral fat (p=0.032) differed when comparing the third month with the sixth and twelfth months. Conclusion: After a kidney transplant, weight gain occurs, especially after the sixth month, reaching 5% per year. Muscle mass increases more than fat mass. People who received kidneys from living donors, those with previous transplants, and those with hypertension and/or cardiovascular disease experience greater weight gain. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Aumento de Peso , Transplante de Rim , Epidemiologia Descritiva , Estudos Longitudinais , Estudos Prospectivos , Espanha , Fatores de Risco
20.
Int J Med Sci ; 4(3): 131-9, 2007 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-17505558

RESUMO

The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by SGLT1 or SGLT2, represents a promising therapeutic approach. Therefore, the aim of the present study was to evaluate the effect of thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected Chinese hamster ovary (CHO) cells expressing human SGLT1 and SGLT2 were used. The inhibitory effect of thioglycosides was assessed in transport studies and membrane potential measurements, using alpha-methyl-glucoside uptake and fluorescence resonance energy transfer, respectively. We found that some thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically, thioglycoside I (phenyl-1'-thio-beta-D-glucopyranoside) inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1'-thio-beta-D-galacto-pyranoside) had a pronounced inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating competitive inhibition as the mechanism of action. Therefore, these thioglycosides represent promising therapeutic agents for the control of hyperglycemia in patients with diabetes.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose , Tioglicosídeos/farmacologia , Animais , Células CHO , Cricetinae , Cricetulus , Humanos , Transportador 2 de Glucose-Sódio , Tioglicosídeos/síntese química , Tioglicosídeos/uso terapêutico
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