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SUMMARY: Glucose has an essential role in the proliferation and survival of testicular tissue. Glucose transporters (GLUTs) are responsible for glucose uptake across cell membranes. In the present work, two main isoforms GLUT1 and GLUT3 were investigated in the testes of Laboratory mouse (BALB/c), Lesser Egyptian jerboa (Jaculus jaculus), Golden hamster (Mesocricetus auratus), and Desert Hedgehog (Paraechinus aethiopicus). Immunofluorescent localization of GLUT1 and GLUT3 showed considerable species differences. The lowest expression of GLUT1 and GLUT3 was localized in the testis of Laboratory mouse (BALB/c), the highest GLUT1 localization was detected in the testis of Lesser Egyptian jerboa (Jaculus jaculus), and the highest GLUT3 immunofluorescent localization was observed in the testis of Hedgehog (Paraechinus aethiopicus). The results imply that GLUT3 is the principal glucose transporter in the studied testes, which is related to species differences. The different immunolocalization of GLUT in examined testes suggests using various transport systems for energy gain in different species.

La glucosa tiene un papel esencial en la proliferación y supervivencia del tejido testicular. Los transportadores de glucosa (GLUT) son responsables de la absorción de glucosa a través de las membranas celulares. En el presente trabajo, se investigaron dos isoformas principales GLUT1 y GLUT3 en los testículos de un ratón de laboratorio (BALB/c), un jerbo egipcio menor (Jaculus jaculus), un hámster dorado (Mesocricetus auratus) y un erizo del desierto (Paraechinus aethiopicus). La localización inmunofluorescente de GLUT1 y GLUT3 mostró diferencias considerables entre especies. La expresión más baja de GLUT1 y GLUT3 se localizó en el testículo del ratón de laboratorio (BALB/c), la localización más alta de GLUT1 se detectó en el testículo del jerbo egipcio menor (Jaculus jaculus) y la localización inmunofluorescente de GLUT3 más alta se observó en el testículo de Erizo (Paraechinus aethiopicus). Los resultados implican que GLUT3 es el principal transportador de glucosa en los testículos estudiados, lo que está relacionado con diferencias entre especies. La diferente inmunolocalización de GLUT en los testículos examinados sugiere el uso de varios sistemas de transporte para ganar energía en diferentes especies.

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Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation.

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Attention and emotion have a positive impact on memory formation, which is related to the activation of the noradrenergic system in the brain. The hippocampus and amygdala are fundamental structures in memory acquisition, which is modulated by noradrenaline through the noradrenergic receptors. Pharmacological studies suggest that memory acquisition depends on the action of both the β3 (β3-AR) and β2 (β2-AR) receptor subtypes. However, the use of animal models with specific knockout for the β3-AR receptor only (β3-ARKO) allows researchers to more accurately assess its role in memory formation processes. In the present study, we evaluated short- and long-term memory acquisition capacity in β3-ARKO mice and wild-type mice at approximately 60 days of age. The animals were submitted to the open field test, the elevated plus maze, object recognition, and social preference. The results showed that the absence of the β3-AR receptor caused no impairment in locomotion and did not cause anxious behavior, but it caused significant impairment of short- and long-term memory compared to wild-type animals. We also evaluated the expression of genes involved in memory consolidation. The mRNA levels for GLUT3, a glucose transporter expressed in the central nervous system, were significantly reduced in the amygdala, but not in the hippocampus of the β3-ARKO animals. Our results showed that β3-AR was involved in the process of acquisition of declarative memory, and its action may be due to the facilitation of glucose absorption in the amygdala.

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UNLABELLED: The effect of hypoglycemia on the contents of glycolytic proteins, activities of enzymes/transporters and flux of HeLa and MCF-7 tumor cells was experimentally analyzed and modeled in silico. After 24 h hypoglycemia (2.5 mm initial glucose), significant increases in the protein levels of glucose transporters 1 and 3 (GLUT 1 and 3) (3.4 and 2.1-fold, respectively) and hexokinase I (HKI) (2.3-fold) were observed compared to the hyperglycemic standard cell culture condition (25 mm initial glucose). However, these changes did not bring about a significant increase in the total activities (Vmax ) of GLUT and HK; instead, the affinity of these proteins for glucose increased, which may explain the twofold increased glycolytic flux under hypoglycemia. Thus, an increase in more catalytically efficient isoforms for two of the main controlling steps was sufficient to induce increased flux. Further, a previous kinetic model of tumor glycolysis was updated by including the ratios of GLUT and HK isoforms, modified pyruvate kinase kinetics and an oxidative phosphorylation reaction. The updated model was robust in terms of simulating most of the metabolite levels and fluxes of the cells exposed to various glycemic conditions. Model simulations indicated that the main controlling steps were glycogen degradation > HK > hexosephosphate isomerase under hyper- and normoglycemia, and GLUT > HK > glycogen degradation under hypoglycemia. These predictions were experimentally evaluated: the glycolytic flux of hypoglycemic cells was more sensitive to cytochalasin B (a GLUT inhibitor) than that of hyperglycemic cells. The results indicated that cancer glycolysis should be inhibited at multiple controlling sites, regardless of external glucose levels, to effectively block the pathway. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.mib.ac.uk/database/achcar/index.html. [Database section added 21 July 2014 after original online publication].

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A lesão periférica de células gigantes (LPCG) e a lesão central de células gigantes (LCCG) são patologias histologicamente semelhantes que acometem a região de cabeça e pescoço. O estudo objetivou analisar a expressão imuno-histoquímica dos marcadores GLUT-1, GLUT-3 e M-CSF em uma série de casos de LPCG e LCCG, na tentativa de compreender os diferentes comportamentos biológicos destas entidades patológicas. A amostra foi constituída por 20 espécimes teciduais de LPCG, 20 de lesão central de células gigantes não agressivas (LCCGNA) e 20 de lesão central de células gigantes agressivas (LCCGA), oriundos do Serviço de Anatomia Patológica da Disciplina de Patologia Oral do Departamento de Odontologia da UFRN. Foi realizada a análise semiquantitativa e qualitativa da expressão imuno-histoquímica dos marcadores nas células gigantes e nas células mononucleares. Em relação ao GLUT-1, verificou-se uma diferença estatisticamente significativa na quantidade de células mononucleares imunomarcadas entre a LPCG e a LCCGNA e entre a LPCG e a LCCGA. Em relação à intensidade da marcação também foi verificado uma diferença estatisticamente significativa tanto para as células mononucleares quanto para as células gigantes entre LPCG e LCCGNA e entre LPCG e LCCGA, nas células gigantes também ocorreu uma diferença estatisticamente significativa entre a LCCGNA e a LCCGA. Em relação ao GLUT-3, foi encontrada uma diferença estatisticamente significativa entre LPCG e LCCGA e entre LCCGNA e LCCGA na quantidade de células mononucleares imunomarcadas. No que concerne à intensidade de marcação para a referida proteína foi verificado uma diferença estatisticamente significativa nas células gigantes entre LPCG e LCCGA. Para o M-CSF foi observada apenas uma diferença estatisticamente significativa na intensidade de marcação nas células mononucleares entre LPCG e LCCGNA e entre LPCG e LCCGA. Com base nestes resultados, pode-se concluir a participação do GLUT-1, GLUT-3 e do M-CSF na patogênese das lesões estudadas. A maior imunomarcação destas proteínas nas células mononucleares evidenciam que tais células desempenham uma maior atividade metabólica e osteoclastogênica, principalmente nas LCCGA. Constatou-se que as células mononucleares estavam mais relacionadas à patogênese das lesões estudadas do que propriamente as células gigantes (AU).

The peripheral giant cell lesion (PGCL) and the central giant cell lesion (CGCL) are lesions histologically similar affecting the head and neck region. The study aimed to analyze the immunohistochemical expression of markers GLUT-1, GLUT-3 and MCSF in a series of cases of PGCL and CGCL, in trying to understand the different biological behavior of these pathologies. The sample consisted of 20 tissue specimens of PGCL 20 central lesion of not aggressive giant cell (CLNAGC) and 20 central lesion of aggressive giant cell (CLAGC), coming from the Pathology Unit of Oral Pathology of the Department of Dentistry of UFRN. Was performed the semi-quantitative and qualitative analysis of immunohistochemical expression of the markers in giant cells and mononuclear cells. In relation to the GLUT-1, it was found a statistically significant difference (p <0.05) in the number of mononuclear cells immunomarked between the PGCL and the CLNAGC and between the PGCL and CLAGC. Regarding the intensity of staining was also observed a statistically significant difference both at the mononuclear cells as in giant cells between PL and CLNAGC and between PGCL and CLAGC, at the giant cells there was also a statistically significant difference between the CLNAGC and CLAGC. In relation to GLUT-3, was found a statistically significant difference between PGCL and CLAGC and between CLAGC and CLNAGC in amount of mononuclear cells immunomarked. Regarding the intensity of labeling for such protein was found a statistically significant difference at the giant cells between PL and CLAGC. To the M-CSF was observed only a statistically significant difference in the intensity of labeling at the mononuclear cells between PGCL and CLNAGC and between PGCL and CLAGC. Based on these results, we can conclude the participation of GLUT-1, GLUT-3 and M-CSF in the pathogenesis of the lesions studied. The bigger immunostaining of these proteins in mononuclear cells show that these cells perform a higher metabolic activity and osteoclastogenic, especially in CLAGC. It was found that the mononuclear cells were more related to the pathogenesis of the studied lesions than properly the giants cells (AU).

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