Navegando por Palavras-chave "transgenic"

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    Genetically altered animals in the study of the metabolic functions of peptide hormone systems
    (Lippincott Williams & Wilkins, 2008-01-01) Mori, Marcelo Alves da Silva [UNIFESP]; Bader, Michael [UNIFESP]; Pesquero, João Bosco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Max Delbruck Ctr Mol Med
    Purpose of reviewHere we review the use of genetically altered animals to address the roles of peptide hormone systems in the modulation of energy homeostasis. Despite the disseminated use of transgenic techniques to establish the functional relevance of several peptide hormone systems, we focus on two multifunctional systems, the renin-angiotensin and the kallikrein-kinin systems. Initially, we explored the background information supporting the functional aspects of these systems, followed by novel knowledge obtained with the phenotypic characterization of genetically altered animals.Recent findingsA role for the renin-angiotensin system in the regulation of adiposity and glucose metabolism has been suggested. Studies using genetically altered animals not only confirmed the physiological relevance of angiotensin 11 in the control of energy homeostasis, but also revealed that the adipose tissue renin-angiotensin system participates in the endocrine modulation of cardiovascular and renal function. On the other hand, the involvement of the kallikrein-kinin system with metabolic processes was not so obvious. Recent reports using genetically altered animals, however, provided strong evidence to support an important role for kinins in the control of glucose homeostasis and energy balance.SummaryHere we present examples of how genetically altered animals contribute to a final postulation of the physiological roles of certain hormone systems, bringing new insights into the field.
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    Increased susceptibility to endotoxic shock in transgenic rats with endothelial overexpression of kinin B(1) receptors
    (Springer, 2008-07-01) Merino, Vanessa F. [UNIFESP]; Todiras, Mihail; Campos, Luciana A.; Saul, Vera; Popova, Elena; Baltatu, Ovidiu C.; Pesquero, Joao B. [UNIFESP]; Bader, Michael; Max Delbruck Ctr Mol Med; Universidade Federal de São Paulo (UNIFESP)
    Two kinin receptors have been described, the inducible B(1) and the constitutive B(2). B(1) receptors are important in cardiovascular homeostasis and inflammation. To further clarify their vascular function, we have generated transgenic rats (TGR(Tie2B(1))) overexpressing the B(1) receptor exclusively in the endothelium. Endothelial cell-specific expression was confirmed by B(1)-agonist-induced relaxation of isolated aorta, which was abolished by endothelial denudation of the vessel. This vasodilatation was mediated by nitric oxide (NO) and K(+) channels. TGR(Tie2B(1)) rats were normotensive but, in contrast to controls, reacted with a marked fall in blood pressure and increased vascular permeability after intravenous injection of a B(1) agonist. After lipopolysaccharide treatment, they present a more pronounced hypotensive response and marked bradycardia associated with increased mortality when compared to non-transgenic control animals. Thus, the transgenic rats overexpressing kinin B(1) receptors exclusively in the endothelium generated in this study support an important role of this receptor in the vasculature during the pathogenesis of endotoxic shock.