RESUMO
The serine-threonine kinase Akt plays a fundamental role in cell survival, metabolism, proliferation, and migration. To keep these essential processes under control, Akt activity and stability must be tightly regulated; otherwise, life-threatening conditions might prevail. Although it is well understood that phosphorylation regulates Akt activity, much remains to be known about how its stability is maintained. Here, we characterize BAG5, a chaperone regulator, as a novel Akt-interactor and substrate that attenuates Akt stability together with Hsp70. BAG5 switches monoubiquitination to polyubiquitination of Akt and increases its degradation caused by Hsp90 inhibition and Hsp70 overexpression. Akt interacts with BAG5 at the linker region that joins the first and second BAG domains and phosphorylates the first BAG domain. The Akt-BAG5 complex is formed in serum-starved conditions and dissociates in response to HGF, coincident with BAG5 phosphorylation. BAG5 knockdown attenuated Akt degradation and facilitated its activation, whereas the opposite effect was caused by BAG5 overexpression. Altogether, our results indicate that Akt stability and signaling are dynamically regulated by BAG5, depending on growth factor availability.
Assuntos
Chaperonas Moleculares , Proteínas Proto-Oncogênicas c-akt , Proteínas de Choque Térmico HSP70/metabolismo , Chaperonas Moleculares/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ubiquitinação , Células HEK293 , Humanos , Animais , CamundongosRESUMO
The presence of unprotected sex activity in women living with type 1 diabetes (T1D) who have insufficient glycemic control should be considered as a specific risky behavior. To evaluate risky behaviors, including unprotected sexual activity, sources of information and knowledge related to reproductive health in adolescents and young adult women with T1D (PwT1D) compared to a group of adolescents and young adult women without diabetes (Comparison group). PwT1D and the Comparison group completed a questionnaire with validated measures that assessed reproductive health. PwT1D (n = 115, age = 17.7 ± 3.2 years) and Comparison group (n = 386, age = 18.3 ± 2.9) were recruited. The proportion of women reporting having sex without any contraceptive was similar in both groups (57.1% and 50%, in PwT1D and Comparison group, respectively). The use of non-effective contraceptive was reported in 63.2% and 63.6% of the PwT1D and Comparison group, respectively. Among PwT1D, parents, formal sex education, and friends were the primary source of information on reproductive health. Low levels of knowledge about diabetes and pregnancy were observed in PwT1D. HbA1c level was associated with having at least one sexual activity without any contraception (OR = 1.63, p = 0.039). PwT1D have similar rates of risky behaviors compared to a Comparison group. Sexual risky behaviors should be especially considered in PwT1D with glycemic control above the optimal level. Parents are an important source of reproductive health information for PwT1D. Use of effective contraception should be reinforced in sexually active PwT1D.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Controle Glicêmico , Comportamentos de Risco à Saúde , Comportamento Sexual , Adolescente , Comportamento do Adolescente , Chile , Comportamento Contraceptivo , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pais , Gravidez , Gravidez na Adolescência , Saúde Reprodutiva , Adulto JovemRESUMO
RESUMEN Para enfrentar el problema de sobrepeso y obesidad en Chile, el enfoque de las políticas públicas debe enfatizar en medidas preventivas, cambiando el entorno en que el individuo se desarrolla para ayudarle a tener un estilo de vida más saludable. La Ley 20.606, tiene por objetivo principal proteger la salud de los chilenos, en especial de los niños, incorporando un marco regulatorio que contempla etiquetado frontal de advertencia en alimentos, prohibición de publicidad dirigida a menores de 14 años y prohibición de venta de alimentos con altos niveles de nutrientes críticos en establecimientos escolares. Las bebidas y néctares azucarados representan una de las fuentes más importantes de azúcares añadidos en la dieta y son de alto consumo por la población chilena. Por tal motivo se revisó la información nutricional y lista de ingredientes en etiquetas de néctares y bebidas de fantasía comercializadas en Chile, antes y después de la promulgación de la Ley 20.606. Los resultados mostraron que las formulaciones de los productos comercializados en el año 2017 se modificaron disminuyendo la concentración de azúcar, sin embargo, se incorporaron edulcorantes no calóricos, los que se encuentran cuestionados por muchos investigadores por posibles efectos adversos para la salud.
ABSTRACT To address the problem of overweight and obesity in Chile, the focus of public policies should emphasize preventive measures to change the environment in which the individual develops and help facilitate a healthier lifestyle. The main objective of the Chilean law 20.606 is to protect the health of Chileans, especially children, by incorporating a regulatory framework that includes a frontal warning labeling on food, a ban on advertising aimed at children under 14 and a ban on the sale of foods with high levels of critical nutrients in schools. Sugar sweetened beverages represent the largest source of added dietary sugars and discretionary calories for Chileans. For this reason, nutritional information and the ingredient list for the nutritional labeling of soft drinks commercialized in Chile were reviewed, before and after enactment of Chilean law 20.606. The results indicated that the formulations of products marketed in 2017 were modified by decreasing the concentration of sugar, however non-caloric sweeteners were incorporated, which are questioned by many researchers for possible adverse effects on health.
Assuntos
Bebidas Gaseificadas , Açúcares , Adoçantes não Calóricos , Legislação sobre Alimentos , Estudo Comparativo , ChileRESUMO
RESUMEN Las algas marinas constituyen un valioso recurso para el desarrollo de productos alimenticios gracias a su composición nutricional, contienen alta concentración de proteínas, vitaminas, minerales y fibra dietética, que en el caso de las algas es particularmente rica en fracción soluble. Las algas además contienen componentes beneficiosos para la salud, como ácidos grasos ω-3 y moléculas bioactivas, con actividad antioxidante, antiinflamatoria, anticancerígena y antidiabética. Además, poseen propiedades tecnológicas, por lo que su incorporación en alimentos procesados y especialmente productos cárnicos como salchichas, hamburguesas, emulsiones cárnicas y otras, resulta beneficioso desde el punto de vista tecnológico y sensorial, siempre que se incorpore en una concentración adecuada.
ABSTRACT Seaweed is a valuable resource for food development due to its nutritional composition. It is high in protein, vitamins, minerals and dietary fiber, and particularly rich in soluble fiber. Seaweed also contains components beneficial to health such as ω-3 PUFAs, bioactive molecules with antioxidants, and anti-inflammatory, anticancer, and antidiabetic activity. It also has technological properties, so its incorporation in processed foods and especially meat products such as sausages, hamburgers, meat emulsions and others would be beneficial from the technological and sensorial point of view, if it is incorporated in an adequate concentration.
Assuntos
Alga Marinha , Ingredientes de Alimentos , Produtos da Carne , Valor NutritivoRESUMO
To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p < 0.01 hypercaloric diet vs standard diet) in the presence of both prazosin and losartan but only in endothelium-intact vessels. Diet-induced obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p < 0.05 vs standard diet). Seven-week hypercaloric diet-induced obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.
Assuntos
Aorta/metabolismo , Dieta/efeitos adversos , Endotélio Vascular/metabolismo , Obesidade/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Vasoconstrição , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ingestão de Energia , Feminino , Técnicas In Vitro , Proteínas de Membrana/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/etiologia , Obesidade/fisiopatologia , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Transdução de Sinais , Fatores de Tempo , Vasoconstrição/efeitos dos fármacosRESUMO
Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e-) vessels. Losartan reduced GDM but not SD e- vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Angiotensina II/administração & dosagem , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Gestacional/induzido quimicamente , Feminino , Humanos , Losartan/administração & dosagem , Fenilefrina/administração & dosagem , Gravidez , Ratos , Vasoconstritores/administração & dosagem , Vasodilatação/efeitos dos fármacosRESUMO
The mammalian target of rapamycin (mTOR) regulates cell growth and survival via two different multiprotein complexes, mTORC1 and mTORC2. The assembly of these serine-threonine kinase multiprotein complexes occurs via poorly understood molecular mechanisms. Here, we demonstrate that GRp58/ERp57 regulates the existence and activity of mTORC1. Endogenous mTOR interacts with GRp58/ERp57 in different mammalian cells. In vitro, recombinant GRp58/ERp57 preferentially interacts with mTORC1. GRp58/ERp57 knockdown reduces mTORC1 levels and phosphorylation of 4E-BP1 and p70(S6K) in response to insulin. In contrast, GRp58/ERp57 overexpression increases mTORC1 levels and activity. A redox-sensitive mechanism that depends on GRp58/ERp57 expression activates mTORC1. Although GRp58/ERp57 is known as an endoplasmic reticulum (ER) resident, we demonstrate its presence at the cytosol, together with mTOR, Raptor, and Rictor as well as a pool of these proteins associated to the ER. In addition, the presence of GRp58/ERp57 at the ER decreases in response to insulin or leucine. Interestingly, a fraction of p70(S6K), but not 4E-BP1, is associated to the ER and phosphorylated in response to serum, insulin, or leucine. Altogether, our results suggest that GRp58/ERp57 is involved in the assembly of mTORC1 and positively regulates mTORC1 signaling at the cytosol and the cytosolic side of the ER.