ABSTRACT
Apolipoprotein (apo) E plays an important role in the whole body cholesterol homeostasis. Recent studies suggest that it may also be involved in the local cholesterol transport in the brain, and influence the pathogenesis of Alzheimer's disease (AD) by interacting with the beta-amyloid protein and brain lipoprotein receptors. Since apoE expression is highest in the brain, next only to the liver and associated with the pathogenesis of AD, we hypothesized that dietary and hormonal intervention, known to regulate hepatic apoE expression may also regulate brain apoE and thereby influence local cholesterol transport. To test this hypothesis, groups of male C57BL mice were fed either regular rodent chow or high fat (HF) and high cholesterol enriched diet for 3 weeks. In a separate study, groups of male mice were administered pharmacological doses of 17-beta estradiol for 5 consecutive days and sacrificed on the 6th day. As expected, HF diet elevated liver apoE mRNA and apoE synthesis. Similar to liver, brain apoE mRNA and synthesis also increased, following HF feeding. Estradiol administration increased liver apoE synthesis without affecting apoE mRNA. Interestingly, estradiol administration also increased the brain apoE synthesis, but without altering the brain apoE mRNA. These studies suggested that dietary cholesterol and estrogen administration elevated the brain apoE by different mechanisms.
Subject(s)
Animals , Apolipoproteins E/biosynthesis , Biological Transport, Active , Brain/metabolism , Cholesterol/biosynthesis , Cholesterol, Dietary/administration & dosage , Estrogens/pharmacology , Female , Gene Expression Regulation , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/biosynthesisABSTRACT
Avaliou-se em 184 indivíduos afro-brasileiros de quatro comunidades de Mato Grosso do Sul, com história familiar de alta prevalência de doenças cardiovasculares e acidente vascular cerebral, a associação entre o polimorfismo I/D do gene da enzima conversora da angiotensina (ECA) com a hipertensão, assim como o defeito dos polimorfismos I/D do peptídeo sinalizador do gene da apo B e da apo E sobre as concentrações séricas de lipídeos. As regiões polimórficas dos genes foram amplificadas pela reação em cadeia pela polimerase e os fragmentos obtidos foram caracterizados por eletroforese em gel de agarose a 2 por cento e poliacrilamida a 10 por cento para o polimorfismo da ECA e peptídeo sinalizador da apo B, respectivamente...
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Alleles , Apolipoproteins B/biosynthesis , Apolipoproteins E/biosynthesis , Arterial Pressure , Cardiovascular Diseases/genetics , Hypertension/physiopathology , Lipids , Polymorphism, Genetic , Stroke/genetics , Electrophoresis, Polyacrylamide Gel , Electrophoresis, Agar Gel/methods , Polymerase Chain Reaction , Data Interpretation, StatisticalABSTRACT
O fígado exerce um importante papel no metabolismo dos quilomicros. É responsável pela síntese de apolipoproteínas (ex., apo AI, apo CII, apo E), lecitina-colesterol-acil-tranferase e lipase de remover os remanescentes de quilomicros da circulaçäo sangüínea. Näo é surpresa portanto que o metabolismo de quilomicros esteja comprometido nas doenças hepáticas tais como hepatite aguda, cirrose e colestase. Assim, sendo, os autores revisaram os aspectos normais do metabolismo dos quilomicros os quais säo essencias para uma melhor compreensäo das alteraçöes lipoprotéicas observadas nas doenças hepáticas