RESUMO
Diabetes and the associated hyperglycemia affect pulmonary physiology and biochemistry inducing endothelial impairment, as the first step in lung vascular dysfunction. Caveolin-1, a characteristic protein of endothelial caveolae, acts as a scaffolding protein involved in signal transduction, cholesterol homeostasis, and vesicular trafficking. To document the effect of hyperglycemia on lung endothelial cells, we designed experiments on streptozotocin-induced diabetes and on double transgenic diabetic mice and investigated (1) the early morphological changes occurring in endothelial cells, (2) the ACE activity and cholesterol content of caveolae-rich membrane microdomains, and (3) the protein and gene expression of caveolin-1. We provide evidence that in diabetic lung, the endothelial cell displays an increased number of caveolae and enlarged surface area and a well-developed synthetic machinery, changes that correlate with an overall augmented ACE activity and cholesterol content and overexpression (gene and protein) of caveolin-1. Targeting the endothelial cell surface molecules modulated by hyperglycemia, such as caveolin-1 and ACE could be an additional therapeutic strategy in diabetes.
Assuntos
Caveolina 1/metabolismo , Diabetes Mellitus Experimental/patologia , Endotélio Vascular/metabolismo , Animais , Caveolina 1/genética , Fracionamento Celular , Extensões da Superfície Celular/ultraestrutura , Colesterol/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/ultraestrutura , Expressão Gênica , Immunoblotting , Pulmão/irrigação sanguínea , Masculino , Camundongos , Camundongos Knockout , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/metabolismo , Regulação para CimaRESUMO
Serotherapy still remains a way of treatment in some diseases, and it could be consider superior to any other mode of action because the protecting substances of the body are the products of the organism itself. The aim of the study was to establish an "in vivo" method for testing the efficacy of therapeutic serum. Hyperimmune serum for influenza A/PR8/34 viral strain, was prepared in sheep, and tested for inhibition of haemagglutination and microneutralisation. Seroprotection was evaluated in mice one day after being challenged with a lethal dose of the same virus. Our study shows that protection occurred in all mice treated with undiluted hyperimmune serum one day post infection (no clinical signs, faster recovery of the body weight after the first three days of the infection, all mice survived).