RESUMEN
A critical step in the uptake of dietary cholesterol by the liver is the binding of remnant lipoprotein particles to receptors in the space of Disse. We have found that increases in the cholesterol content of hepactocyte membranes reduces the binding of beta-very low density lipoproteins (beta-VLDL) and decreases internalization. This increase in membrane cholesterol of human hepatoma cells (HepG2) produces a similar effect on binding to primary human fibroblasts. However, receptor-negative familial hypercholesterolemic (FH) fibroblasts lack the ability to respond to membrane cholesterol modification. A polyclonal antibody directed against the C-terminus region of the apo-B,E-(LDL) receptor importantly affects the internalization process, suggesting that protein-protein interactions consolidate the pattern formation of receptors, a process that triggers lipoprotein internalization. We propose that cholesterol interferes with this pattern formation by affecting the lateral movement and organization of the receptors.
Asunto(s)
Apolipoproteínas E/metabolismo , Colesterol en la Dieta/metabolismo , Lipoproteínas VLDL/metabolismo , Receptores de LDL/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos/fisiología , Apolipoproteínas E/aislamiento & purificación , Sitios de Unión , Carcinoma Hepatocelular , Línea Celular , Membrana Celular/metabolismo , Células Cultivadas , Colesterol/metabolismo , Fibroblastos , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Cinética , Lipoproteínas VLDL/aislamiento & purificación , Liposomas , Neoplasias Hepáticas , Lípidos de la Membrana/metabolismo , Modelos Biológicos , Datos de Secuencia Molecular , Conejos , Receptores de LDL/química , Receptores de LDL/inmunología , Proteínas Recombinantes/metabolismo , Transfección , Células Tumorales CultivadasRESUMEN
Subungual keratoacanthoma is a rare, benign tumor of the digits. Patients present with progressive fusiform swelling, erythema, and tenderness, usually affecting a single digit on the radial side of the hand. A cup-shaped lytic lesion of the distal phalanx is a uniform finding on radiography. Delay in diagnosis and misdiagnosis are common because of the rarity of the lesion and difficulties with histological differentiation from subungual squamous cell carcinoma. Accurate diagnosis requires a high index of suspicion, a careful history, and histological evaluation. The natural progression of the disease appears to be continued growth with ongoing destruction of the distal phalanx. Proper treatment involves surgical removal of the mass by curettage and close follow-up for at least 2 years to monitor for local recurrence.