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1.
Cell Mol Neurobiol ; 43(3): 1237-1265, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35798933

RESUMO

Our previous studies showed more severe experimental autoimmune encephalomyelitis (EAE) in male compared with female adult rats, and moderating effect of propranolol-induced ß-adrenoceptor blockade on EAE in females, the effect associated with transcriptional stimulation of Nrf2/HO-1 axis in spinal cord microglia. This study examined putative sexual dimorphism in propranolol action on EAE severity. Propranolol treatment beginning from the onset of clinical EAE mitigated EAE severity in rats of both sexes, but to a greater extent in males exhibiting higher noradrenaline levels and myeloid cell ß2-adrenoceptor expression in spinal cord. This correlated with more prominent stimulatory effects of propranolol not only on CX3CL1/CX3CR1/Nrf2/HO-1 cascade, but also on Stat3/Socs3 signaling axis in spinal cord microglia/myeloid cells (mirrored in the decreased Stat3 and the increased Socs3 expression) from male rats compared with their female counterparts. Propranolol diminished the frequency of activated cells among microglia, increased their phagocyting/endocyting capacity, and shifted cytokine secretory profile of microglia/blood-borne myeloid cells towards an anti-inflammatory/neuroprotective phenotype. Additionally, it downregulated the expression of chemokines (CCL2, CCL19/21) driving T-cell/monocyte trafficking into spinal cord. Consequently, in propranolol-treated rats fewer activated CD4+ T cells and IL-17+ T cells, including CD4+IL17+ cells coexpressing IFN-γ/GM-CSF, were recovered from spinal cord of propranolol-treated rats compared with sex-matched saline-injected controls. All the effects of propranolol were more prominent in males. The study as a whole disclosed that sexual dimorphism in multiple molecular mechanisms implicated in EAE development may be responsible for greater severity of EAE in male rats and sexually dimorphic action of substances affecting them. Propranolol moderated EAE severity more effectively in male rats, exhibiting greater spinal cord noradrenaline (NA) levels and myeloid cell ß2-adrenoceptor (ß2-AR) expression than females. Propranolol affected CX3CR1/Nrf2/HO-1 and Stat3/Socs3 signaling axes in myeloid cells, favored their anti-inflammatory/neuroprotective phenotype and, consequently, reduced Th cell reactivation and differentiation into highly pathogenic IL-17/IFN-γ/GM-CSF-producing cells.


Assuntos
Encefalomielite Autoimune Experimental , Ratos , Feminino , Masculino , Animais , Encefalomielite Autoimune Experimental/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-17/metabolismo , Propranolol , Doenças Neuroinflamatórias , Caracteres Sexuais , Fator 2 Relacionado a NF-E2/metabolismo , Medula Espinal/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Norepinefrina , Receptores Adrenérgicos/metabolismo
2.
Mutagenesis ; 38(1): 3-12, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36082791

RESUMO

In this study, the possible 'vector effect' within the exposure of Mediterranean mussels (Mytilus galloprovincialis) to polystyrene microplastics with adsorbed fluoranthene was investigated by applying the multibiomarker approach. The major focus was placed on genotoxicological endpoints as to our knowledge there are no literature data on the genotoxicity of polystyrene microparticles alone or with adsorbed fluoranthene in the selected experimental organisms. DNA damage was assessed in haemocytes by comet assay and micronucleus test. For the assessment of neurotoxicity, acetylcholinesterase activity was measured in gills. Glutathione S-transferase was assessed in gills and hepatopancreas since these enzymes are induced for biotransformation and excretion of lipophilic compounds such as hydrocarbons. Finally, differences in physiological response within the exposure to polystyrene particles, fluoranthene, or particles with adsorbed fluoranthene were assessed by the variation of heart rate patterns studied by the noninvasive laser fibre-optic method. The uniform response of individual biomarkers within the exposure groups was not recorded. There was no clear pattern in variation of acetylcholinesterase or glutathione S-transferase activity which could be attributed to the treatment. Exposure to polystyrene increased DNA damage which was detected by the comet assay but was not confirmed by micronucleus formation. Data of genotoxicity assays indicated differential responses among the groups exposed to fluoranthene alone and fluoranthene adsorbed to polystyrene. Change in the heart rate patterns within the studied groups supports the concept of the Trojan horse effect within the exposure to polystyrene particles with adsorbed fluoranthene.


Assuntos
Mytilus , Poluentes Químicos da Água , Animais , Mytilus/metabolismo , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Plásticos/metabolismo , Plásticos/farmacologia , Dano ao DNA , Glutationa Transferase/genética , Poluentes Químicos da Água/farmacologia , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismo
3.
Int J Mol Sci ; 24(7)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37047558

RESUMO

After being discovered over a century ago, insulin was long considered to be a hormone exclusively produced by the pancreas. Insulin presence was later discovered in the brain, which was originally accounted for by its transport across the blood-brain barrier. Considering that both insulin mRNA and insulin were detected in the central nervous system (CNS), it is now known that this hormone is also synthesized in several brain regions, including the hypothalamus, hippocampus, cerebral and cerebellar cortex, and olfactory bulb. Although many roles of insulin in the CNS have been described, it was initially unknown which of them could be attributed to brain-derived and which to pancreatic insulin or whether their actions in the brain overlap. However, more and more studies have been emerging lately, focusing solely on the roles of brain-derived insulin. The aim of this review was to present the latest findings on the roles of brain-derived insulin, including neuroprotection, control of growth hormone secretion, and regulation of appetite and neuronal glucose uptake. Lastly, the impairment of signaling initiated by brain-derived insulin was addressed in regard to memory decline in humans.


Assuntos
Sistema Nervoso Central , Insulina , Humanos , Insulina/metabolismo , Sistema Nervoso Central/metabolismo , Encéfalo , Aprendizagem , Barreira Hematoencefálica/metabolismo , Insulina Regular Humana
4.
Environ Monit Assess ; 195(10): 1237, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733141

RESUMO

Lakes and reservoirs are the main water resources for household, irrigation, and industrial use. Hence, it is necessary to control water pollution and have reliable information on water quality, which refers to its suitability for a particular purpose. The main objective of this study was to evaluate the suitability of water for drinking and irrigation purposes from ten artificial lakes on the territory of the Republic of Serbia. The physicochemical parameters were determined using standard analytical methods, whereas the optical emission spectrometry with inductively coupled plasma, ICP-OES, was used to determine the concentrations of 23 macro-, micro-, and trace elements in water. Health risk indices of drinking water and its suitability for irrigation purposes were evaluated. The results of physicochemical parameters, except for total organic matter, indicated that most samples were within the recommended values. Among analyzed elements, the concentration of Mg was elevated in the water of the lakes Srebrno and Prvonek. The results of health risk assessment clearly showed that there was no acute health risk (HQA < 1), whereas long-term risk (HQL) in the studied lakes was observed with respect to As (lakes Grliste and Srebrno), Mn (lakes Srebrno and Prvonek), Ni (Lake Vrutci), and Sr (Lake Grliste). The irrigation criteria indicated that the water from the examined lakes had satisfactory quality for this purpose, except for residual sodium carbonates (RSC). This criterion indicated low quality or unsuitability of the water in 7 lakes. The main outcomes provided valuable information on the suitability of water from the artificial lakes for intended uses.


Assuntos
Oligoelementos , Sérvia , Lagos , Monitoramento Ambiental , Indústrias
5.
J Enzyme Inhib Med Chem ; 37(1): 151-167, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34894940

RESUMO

An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1-3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.


Assuntos
Antiprotozoários/farmacologia , Inibidores Enzimáticos/farmacologia , Indazóis/farmacologia , Leishmania major/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Indazóis/síntese química , Indazóis/química , Leishmania major/enzimologia , Modelos Moleculares , Estrutura Molecular , NADH NADPH Oxirredutases/antagonistas & inibidores , NADH NADPH Oxirredutases/metabolismo , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
6.
Mar Drugs ; 19(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34564162

RESUMO

Seaweeds are industrially exploited for obtaining pigments, polysaccharides, or phenolic compounds with application in diverse fields. Nevertheless, their rich composition in fiber, minerals, and proteins, has pointed them as a useful source of these components. Seaweed proteins are nutritionally valuable and include several specific enzymes, glycoproteins, cell wall-attached proteins, phycobiliproteins, lectins, or peptides. Extraction of seaweed proteins requires the application of disruptive methods due to the heterogeneous cell wall composition of each macroalgae group. Hence, non-protein molecules like phenolics or polysaccharides may also be co-extracted, affecting the extraction yield. Therefore, depending on the macroalgae and target protein characteristics, the sample pretreatment, extraction and purification techniques must be carefully chosen. Traditional methods like solid-liquid or enzyme-assisted extraction (SLE or EAE) have proven successful. However, alternative techniques as ultrasound- or microwave-assisted extraction (UAE or MAE) can be more efficient. To obtain protein hydrolysates, these proteins are subjected to hydrolyzation reactions, whether with proteases or physical or chemical treatments that disrupt the proteins native folding. These hydrolysates and derived peptides are accounted for bioactive properties, like antioxidant, anti-inflammatory, antimicrobial, or antihypertensive activities, which can be applied to different sectors. In this work, current methods and challenges for protein extraction and purification from seaweeds are addressed, focusing on their potential industrial applications in the food, cosmetic, and pharmaceutical industries.


Assuntos
Fracionamento Químico/métodos , Hidrolisados de Proteína/isolamento & purificação , Hidrolisados de Proteína/uso terapêutico , Peptídeos/isolamento & purificação , Peptídeos/uso terapêutico , Fenóis/isolamento & purificação , Polissacarídeos , Alga Marinha/química
7.
Ecotoxicol Environ Saf ; 208: 111607, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396127

RESUMO

The present study aimed to explore the effect of synthetic and naturally occurring chelators, EDTA and citric acid (CA), respectively, on changes in physiological and biochemical factors including cell death, level of mercury ions accumulation, malondialdehyde (MDA) content, total phenol and total flavonoids, anthocyanins and DPPH free radical scavenging activity, in the leaves of okra (Abelmoschus esculentus L.) plants exposed to mercury stress. In addition, polyphenolic compounds profile was assessed by high-performance liquid chromatography. The okras were planted in completely controlled hydroponic conditions (Hoagland solution). After they reached the four-leaf stage, they were treated simultaneously with different concentrations of HgCl2, EDTA and CA chelators, and their combination for one month. At the stage of maturity, the physiological and biochemical factors of the plant leaves were measured. The results showed that with the application of higher concentration of HgCl2, cell death, level of shoot and root Hg2+ content and root MDA, total phenols and total flavonoids, anthocyanin content, and DPPH free radical scavenging activity were increased. Also, the results indicated that okra plants have high biomass and a high rate of Hg mobilization and accumulation in the shoot versus the roots (TF=2.152 for the plants treated with 60 mg L-1 Hg2+), hence, can be considered as Hg hyperaccumulator plant for the phytoremediation of Hg-polluted soils and waters. In the Hg-treated plants changes in their phenolic profile were induced, and the increase of chlorogenic acid, rosmaric acid, apigenin, quercetin and rutin content was observed. The application of EDTA and CA improved the toxic effects of Hg2+, by modifying phenolic compounds, chelating Hg2+, and its proper compartmentation, while EDTA outperformed CA in this respect. Based on the results, it could be concluded that due to the high biomass and growth of okra in the presence of Hg2+, this plant is suitable for phytoremediation of soil and water contaminated with mercury. In addition, EDTA and CA can play a significant role in removing this toxic metal through transferring it from the culture medium to the plant.


Assuntos
Abelmoschus/efeitos dos fármacos , Ácido Cítrico/farmacologia , Ácido Edético/farmacologia , Mercúrio/toxicidade , Fenóis/metabolismo , Poluentes do Solo/toxicidade , Abelmoschus/crescimento & desenvolvimento , Abelmoschus/metabolismo , Fenômenos Bioquímicos/efeitos dos fármacos , Biodegradação Ambiental , Biomassa , Malondialdeído/metabolismo , Mercúrio/análise , Fenóis/análise , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Solo/química , Poluentes do Solo/análise
8.
Pharmacol Res ; 155: 104723, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32105756

RESUMO

Diabetes mellitus (DM) is a chronic metabolic disease which causes millions of death all over the world each year, and its incidence is on increase. The most prevalent form, type 2 DM, is characterized by insulin resistance and ß-cell dysfunction, whereas type 1 DM is due to insulin deficiency as a result of ß-cell destruction. Various classes of synthetic drugs have been developed to regulate glucose homeostasis and combat the development of late-diabetic complications. However, several of these chemical agents are either sub-optimal in their effect and/or may have side effects. Biologically, alkaloids unveiled a wide range of therapeutic effects including anti-diabetic properties. The chemical backbones of these compounds have the potential to interact with a wide range of proteins involved in glucose homeostasis, and thus they have received increasing attention as reliable candidates for drug development. This review sets out to investigate the anti-diabetic potential of plant alkaloids (PAs), and therefore, scientific databases were comprehensively screened to highlight the biological activity of 78 PAs with a considerable anti-diabetic profile. There are not enough clinical data available for these phytochemicals to follow their fingerprint in human, but current studies generally recommending PAs as potent α-glucosidase inhibitors. Except for some classes of monoterpene alkaloids, other compounds showed similar features as well as the presently available anti-diabetic drugs such as amino sugars and other relevant drugs. Moreover, the evidence suggests that PAs have the potential to be used as alternative additives for the treatment of DM, however, further in vitro and in vivo studies are needed to validate these findings.


Assuntos
Alcaloides/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Animais , Humanos , Compostos Fitoquímicos/uso terapêutico , Fitoterapia
9.
Mol Cell Neurosci ; 94: 11-22, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30404024

RESUMO

In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid ß plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mice in this model, but whether this extends to synaptic function is unknown. We investigated the influence of background strain on basal synaptic transmission and long-term potentiation (LTP) in the hippocampus of TgCRND8 mice (13-16 months) on hybrid backgrounds of (129SvEv/Tac) x (C3H/C57/129SvEv/Tac) (aka "129") or (C57) x (C3H/C57) (aka "C3H"). In littermate controls, basal synaptic transmission was significantly reduced, whereas the amplitude of excitatory postsynaptic potentials was significantly higher after LTP induction in 129 vs. C3H mice. In 129 TgCRND8 mice, deficits in hippocampal LTP were more severe than in C3H TgCRND8 relative to controls. Compared to controls, network excitability was decreased in transgenics from both strains. These data suggest that 129 TgCRND8 mice are the more appropriate model to evaluate the efficacy of potential AD treatments on synaptic function, owing to their significant deficit in LTP. Such studies are critical in order to improve the translational capacity of basic science research.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/fisiologia , Camundongos , Transmissão Sináptica/fisiologia
10.
Ecotoxicol Environ Saf ; 190: 110058, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31864118

RESUMO

Worldwide, among the forest products, wild edible mushrooms constitute an important part because they represent food source as well as income source for many local communities. Thirteen essential elements (Ca, Co, Cr, Cu, Fe, K, Mg, Mn and Zn) and non-essential elements (Al, Cd, Ni and Pb) in wild edible mushrooms from six families (Agaricaceae, Auriculariaceae, Hygrophoraceae, Russulaceae, Suillaceae, and Tricholomataceae) originated from the Mediterranean region of Turkey were determined. Major element was K, followed by Ca, Mg, Fe and Al. Concentrations of detected elements were in the range from 0.05 mg/kg (Co) to 141,400 mg/kg (K). Health Risk Index for elements that may pose health problems indicated that safe limits were exceeded for Cd (L. nuda, L. decastes, M. exscissa, R. albonigra, R. delica and T. terreum), Ni (A. auricula-judae and S. luteus) as well as for Fe (A. auricula-judae and M. paedida). In Arpacik village and Deliosman village areas the highest number of wild edible mushrooms with HRI>1 was collected. The differences and similarities between mushroom species were established by Principal Component Analysis and Hierarchical Component Analysis.


Assuntos
Agaricales/química , Metais/análise , Basidiomycota/química , Metais/toxicidade , Medição de Risco , Turquia
11.
Phytother Res ; 34(2): 315-328, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31713286

RESUMO

Convolvulus genus is a representative of the family of Convolvulaceae. Convolvulus plants are broadly distributed all over the world and has been used for many centuries as herbal medicine. Convolvulus genus contains various phytochemicals such as flavonoids, alkaloids, carbohydrates, phenolic compounds, mucilage, unsaturated sterols or terpenes, resin, tannins, lactones, and proteins. This review highlights the phytochemical composition, antimicrobial and antioxidant activities, application as food preservative, traditional medicine use, anticancer activities, and clinical effectiveness in human of Convolvulus plants. All the parts of Convolvulus plants possess therapeutic benefits; preliminary pharmacological data validated their use in traditional medicine. However, further preclinical and clinical experiments are warranted before any application in human health.


Assuntos
Convolvulus/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Convolvulus/classificação , Conservantes de Alimentos , Humanos , Medicina Tradicional , Fitoterapia , Plantas Medicinais/classificação
12.
Neurobiol Dis ; 127: 264-277, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30878533

RESUMO

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles and amyloid beta are classic hallmarks of AD, the earliest deficits in AD progression may be caused by unknown factors. One suspected factor has to do with brain energy metabolism. To investigate this factor, brain metabolic activity in 3xTg-AD mice and age-matched controls were measured with FDG-PET. Significant hypometabolic changes (p < .01) in brain metabolism were detected in the cortical piriform and insular regions of AD brains relative to controls. These regions are associated with olfaction, which is a potential clinical marker for AD progression as well as neurogenesis. The activity of the terminal component of the mitochondrial respiratory chain (complex IV) and the expression of complex I-V were significantly decreased (p < .05), suggesting that impaired metabolic activity coupled with impaired oxidative phosphorylation leads to decreased mitochondrial bioenergetics and subsequent Neurodegeneration. Although there is an association between neuroinflammatory pathological markers (microglial) and hypometabolism in AD, there was no association found between neuropathological (Aß, tau, and astrocytes) and functional changes in AD sensitive brain regions, also suggesting that brain hypometabolism occurs prior to AD pathology. Therefore, targeting metabolic mechanisms in cortical piriform and insular regions at early stages may be a promising approach for preventing, slowing, and/or blocking the onset of AD and preserving neurogenesis.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Mitocôndrias/metabolismo , Emaranhados Neurofibrilares/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Fosforilação Oxidativa , Proteínas tau/metabolismo
13.
Cell Immunol ; 336: 48-57, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30600100

RESUMO

Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4+ T-cell (auto)immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (ß-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4+ T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of ß2-adrenoceptor-expressing CD4+ T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4+ lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1ß and IL-23/p19 expression and IL-17+ CD4+ cell frequency, but enhanced IL-17 production only in male rat CD4+ lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, ß-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Encefalomielite Autoimune Experimental/imunologia , Norepinefrina/fisiologia , Receptores Adrenérgicos beta/fisiologia , Caracteres Sexuais , Antagonistas Adrenérgicos beta/farmacologia , Animais , Feminino , Interleucina-17/análise , Ativação Linfocitária , Masculino , Proteína Básica da Mielina/farmacologia , Ratos
14.
Neurochem Res ; 44(2): 388-399, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30460639

RESUMO

Our group previously reported that 6-h fasting increased both insulin II mRNA expression and insulin level in rat hypothalamus. Given that insulin effects on central glucose metabolism are insufficiently understood, we wanted to examine if the centrally produced insulin affects expression and/or regional distribution of glucose transporters, and glycogen stores in the hypothalamus during short-term fasting. In addition to determining the amount of total and activated insulin receptor, glucose transporters, and glycogen, we also studied distribution of insulin receptors and glucose transporters within the hypothalamus. We found that short-term fasting did not affect the astrocytic 45 kDa GLUT1 isoform, but it significantly increased the amount of endothelial 55 kDa GLUT1, and neuronal GLUT3 in the membrane fractions of hypothalamic proteins. The level of GLUT2 whose presence was detected in neurons, ependymocytes and tanycytes was also elevated. Unlike hepatic glycogen which was decreased, hypothalamic glycogen content was not changed after 6-h fasting. Our findings suggest that neurons may be given a priority over astrocytes in terms of glucose supply even during the initial phase of metabolic response to fasting. Namely, increase in glucose influx into the brain extracellular fluid and neurons by increasing the translocation of GLUT1, and GLUT3 in the cell membrane may represent the first line of defense in times of scarcity. The absence of co-localization of these membrane transporters with the activated insulin receptor suggests this process takes place in an insulin-independent manner.


Assuntos
Astrócitos/metabolismo , Células Endoteliais/metabolismo , Jejum , Neurônios/metabolismo , Animais , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hipotálamo/metabolismo , Masculino , Neuroglia/metabolismo , Ratos Wistar , Ativação Transcricional/fisiologia
16.
Mol Cell Neurosci ; 90: 49-59, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29802939

RESUMO

AIMS: Abnormalities in mitochondrial function under diabetic conditions can lead to deficits in function of cortical neurons and their support cells exhibiting a pivotal role in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. We aimed to assess mitochondrial respiration rates and membrane potential or H2O2 generation simultaneously and expression of proteins involved in mitochondrial dynamics, ROS scavenging and AMPK/SIRT/PGC-1α pathway activity in cortex under diabetic conditions. METHODS: Cortical mitochondria from streptozotocin (STZ)-induced type 1 diabetic rats or mice, and aged-matched controls were used for simultaneous measurements of mitochondrial respiration rates and mitochondrial membrane potential (mtMP) or H2O2 using OROBOROS oxygraph. Measurements of enzymatic activities of respiratory complexes were performed using spectophotometry. Protein levels in cortical mitochondria and homogenates were determined by Western blotting. RESULTS: Mitochondrial coupled respiration rates and FCCP-induced uncoupled respiration rates were significantly decreased in mitochondria of cortex of STZ-diabetic rats compared to controls. The mtMP in the presence of ADP was significantly depolarized and succinate-dependent respiration rates and H2O2 were significantly diminished in cortical mitochondria of diabetic animals compared to controls, accompanied with reduced expression of CuZn- and Mn-superoxide dismutase. The enzymatic activities of Complex I, II, and IV and protein levels of certain components of Complex I and II, mitofusin 2 (Mfn2), dynamin-related protein 1 (DRP1), P-AMPK, SIRT2 and PGC-1α were significantly diminished in diabetic cortex. CONCLUSION: Deficits in mitochondrial function, dynamics, and antioxidant capabilities putatively mediated through sub-optimal AMPK/SIRT/PGC-1α signaling, are involved in the development of early sub-clinical neurodegeneration in the cortex under diabetic conditions.

17.
Chem Biodivers ; 16(4): e1800693, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707488

RESUMO

True truffles (Tuber sp.) that establish ectomycorrhizal symbiosis (ECM) with trees in the Mediterranean and temporal regions have species specific abilities to assimilate soil born elements. Suitable habitats are usually inhabited by few truffle species, while distinguishing their symbiotic potentials appeared very difficult. Two species that commonly inhabit riparian forests in Serbia are the most prized one, Tuber magnatum Pico (Piedmont white truffle) and not so highly valued Tuber brumale Vitt. In order to assess potential differences between their assimilation and accumulation abilities, the differences between contents of elements that may be the subjects of the symbiotic trade between the host plant and fungi were evaluated in accumulation target (ascocarps) and their source (the soil). Essential (K, Na, Ca, Mg, Fe, P, S, and Zn) and essential trace elements (Co, Cr, Cu, Mn, and Se) in truffles and soil samples were determined by means of inductively coupled plasma with optical emission spectrometry (ICP-OES). Their concentrations (mg/kg) in ascocarps were in the range from 1.364±0.591 (Cr) to 10760.862±16.058 (K), while in soil ranged from 23.035±0.010 (Cr) to 20809.300±122.934 (Fe). Element accumulation potential (bioaccumulation factor) was calculated in the system truffle/soil. The statistical approaches were used for establishing the differences, while the possible differentiation between symbiotic potentials of two mycelia in the defined soil conditions was discussed.


Assuntos
Metais/análise , Micorrizas/química , Tubérculos/química , Sérvia , Especificidade da Espécie
18.
Molecules ; 24(13)2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31284600

RESUMO

Grape brandy, known as 'Lozovaca', is one of the most produced alcoholic beverages in the Republic of Serbia. Muscat cultivars are highly priced in grape brandy manufacturing. Among the numerous factors, cultivar-specific characteristics have a significant influence on its quality and aroma profile. Pectolytic enzymes play a part in increasing intensity of the prefermentative aroma by hydrolysis of terpenic glycosides, from which the compounds that contribute to the aroma of brandy are released. In this study, grape brandy samples were produced from five Muscat table grapevine cultivars (Vitis vinifera L.) namely, Early Muscat, Radmilovac Muscat, Banat Muscat, Italia Muscat, and Muscat Hamburg, with the addition of pectolytic enzyme in two different concentrations or without it (control). A total of 58 volatile aroma compounds were detected by means of combined gas chromatographic-mass spectrometric (GC/MS) method. Ethyl esters of C8-C18 fatty acids (21) and terpene (16) compounds were considerably more abundant in all grape brandy samples compared to the other volatile compounds identified. Pectolytic enzyme, positively affected terpenes content in the brandy of all studied cultivars. The similarities between brandy samples produced from Muscat Hamburg (MH) and other Muscat cultivars may be attributed to the parentage of MH to those cultivars.


Assuntos
Bebidas Alcoólicas/análise , Odorantes/análise , Vitis/química , Compostos Orgânicos Voláteis/análise , Análise por Conglomerados , Cromatografia Gasosa-Espectrometria de Massas , Análise de Componente Principal
19.
Learn Mem ; 25(2): 54-66, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29339557

RESUMO

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform (P < 0.05) and increased the time spent in the target quadrant (P < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.


Assuntos
Creatina/administração & dosagem , Suplementos Nutricionais , Hipocampo/metabolismo , Mitocôndrias/metabolismo , Memória Espacial/fisiologia , Animais , Metabolismo Energético , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Plasticidade Neuronal/fisiologia , Oxigênio/metabolismo , Distribuição Aleatória
20.
Plant Foods Hum Nutr ; 73(4): 295-301, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30168039

RESUMO

The gut microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms which are shown to influence host metabolism and immune homeostasis. This study investigated the effects of virgin coconut oil on the weekly fasting glycaemia, daily food and water intake and weekly body mass gain over 16 weeks, as well as the changes in composition of gut microbiota in both non-diabetic and alloxan-induced diabetic rats. Although the intake of virgin coconut oil did not decrease the diabetes-induced hyperglycemia, it affected the secondary parameters, such as food and water intake and average body mass gain. Furthermore, its potential to positively affect the fecal microbiome was proved, since it significantly increased the abundance of probiotic bacteria, such as Lactobacillus, Allobaculum and Bifidobacterium species.


Assuntos
Óleo de Coco/farmacologia , Diabetes Mellitus Experimental/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/microbiologia , Ingestão de Alimentos/efeitos dos fármacos , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Masculino , Probióticos , Ratos Wistar
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