Thyroid Hormone Increases TGF-β1 in Cardiomyocytes Cultures Independently of Angiotensin II Type 1 and Type 2 Receptors

TH-induced cardiac hypertrophy in vivo is accompanied by increased cardiac Transforming Growth Factor-β1 (TGF-β1) levels, which is mediated by Angiotensin II type 1 receptors (AT1R) and type 2 receptors (AT2R). However, the possible involvement of this factor in TH-induced cardiac hypertrophy is unknown. In this study we evaluated whether TH is able to modulate TGF-β1 in isolated cardiac, as well as the possible contribution of AT1R and AT2R in this response. The cardiac fibroblasts treated with T3 did not show alteration on TGF-β1 expression. However, cardiomyocytes treated with T3 presented an increase in TGF-β1 expression, as well as an increase in protein synthesis. The AT1R blockade prevented the T3-induced cardiomyocyte hypertrophy, while the AT2R blockage attenuated this response. The T3-induced increase on TGF-β1 expression in cardiomyocytes was not changed by the use of AT1R and AT2R blockers. These results indicate that Angiotensin II receptors are not implicated in T3-induced increase on TGF-β expression and suggest that the trophic effects exerted by T3 on cardiomyocytes are not dependent on the higher TGF-β1 levels, since the AT1R and AT2R blockers were able to attenuate the T3-induced cardiomyocyte hypertrophy but were not able to attenuate the increase on TGF-β1 levels promoted by T3

Caracterização parcial da hidrólise de ATP, ADP e AMP em fração microssomal cardíaca de ratos adultos

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Caracterização parcial da hidrólise de ATP, ADP e AMP em fração microssomal cardíaca de ratos adultos

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Impact of corporate R&D on efficiency in OECD industries

Efficiency and productivity have always been a key issue in economic science. The analysis of the impact of R&D (Research and Development) has been extensively studied in industries and countries of more or less aggregated level. This paper aims to investigate the impact of corporate R&D in performance of low-tech industries, medium-tech and high-tech in OECD countries. This paper aims to answer the questions: Is the impact of R&D significant for all types of industries? If so, what are the differences and the magnitude of these effects in each of these types of industries? To this end, an unbalanced dataset from 2000 to 2011 was collected for the main countries of Europe and the United States concerning low, medium and high-tech to analyse the impact of the magnitude of corporate R&D and capital accumulation on productivity of these industries. The productivity of industries was measured by stochastic parametric frontier functions, in order to measure the efficiency of R&D and accumulation of capital on labour productivity. The main results highlight the impact of corporate R&D on productivity of high-tech industries, but for other industries those relations are not clear. However, capital accumulation became crucial on low technology to improve their performance. These results, although needing to include a more extensive dataset of industries across countries, refer the need for policy and decision makers to allocate public funds for R&D in high-tech industries, while the investment in capital seems crucial, particularly in low-tech industries to improve the productivity.info:eu-repo/semantics/publishedVersio

Emerging role of angiotensin type 2 receptor (AT2R)/Akt/NO pathway in vascular smooth muscle cell in the hyperthyroidism

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 µmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo; grants 06/61523-7 and 06/54064-6)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paul

Mifepristona (ru38486) impede o efeito antiproliferativo da dexametasona em linhagem de glioma c6 de rato

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Caracterização cinética de uma NTPDase e uma 5'nucleotidase em fração sinaptossomal crua isolada de coração de rato

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Caracterização cinética de uma NTPDase e uma 5'nucleotidase em fração sinaptossomal crua isolada de coração de rato

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Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3 beta/mTOR signaling pathway

Several studies have implicated the renin angiotensin system in the cardiac hypertrophy induced by thyroid hormone. However, whether Angiotensin type 1 receptor (AT(1)R) is critically required to the development of T(3)-induced cardiomyocyte hypertrophy as well as whether the intracellular mechanisms that are triggered by AT(1)R are able to contribute to this hypertrophy model is unknown. To address these questions, we employed a selective small interfering RNA (siRNA, 50 nM) or an AT(1)R blocker (Losartan, 1 mu M) to evaluate the specific role of this receptor in primary cultures of neonatal cardiomyocytes submitted to T(3) (10 nM) treatment. The cardiomyocytes transfected with the AT(1)R siRNA presented reduced mRNA (90%, P < 0.001) and protein (70%, P < 0.001) expression of AT(1)R. The AT(1)R silencing and the AT(1)R blockade totally prevented the T(3)-induced cardiomyocyte hypertrophy, as evidenced by lower mRNA expression of atrial natriuretic factor (66%, P < 0.01) and skeletal alpha-actin (170%, P < 0.01) as well as by reduction in protein synthesis (85%, P < 0.001). The cardiomyocytes treated with T(3) demonstrated a rapid activation of Akt/GSK-3 beta/mTOR signaling pathway, which was completely inhibited by the use of PI3K inhibitors (LY294002, 10 mu M and Wortmannin, 200 nM). In addition, we demonstrated that the AT(1)R mediated the T(3)-induced activation of Akt/GSK-3 beta/mTOR signaling pathway, since the AT(1)R silencing and the AT(1)R blockade attenuated or totally prevented the activation of this signaling pathway. We also reported that local Angiotensin I/II (Ang I/II) levels (120%, P < 0.05) and the AT(1)R expression (180%, P < 0.05) were rapidly increased by T(3) treatment. These data demonstrate for the first time that the AT(1)R is a critical mediator to the T(3)-induced cardiomyocyte hypertrophy as well as to the activation of Akt/GSK-3 beta/mTOR signaling pathway. These results represent a new insight into the mechanism of T(3)-induced cardiomyocyte hypertrophy, indicating that the Ang I/II-AT(1)R-Akt/GSK-3 beta/mTOR pathway corresponds to a potential mediator of the trophic effect exerted by T(3) in cardiomyocytes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao PauloCNPq Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq