ABSTRACT
PURPOSE: A family of organic anion transporters (OAT) has been identified, and several isoforms have been reported. The regulatory mechanisms of OATs functions, however, still remain to be elucidated. The rat OAT1 contributes to move a number of negatively-charged organic compounds between cells and their extracellular milieu. Caveolin (Cav) also plays a role in membrane transport. To address this issue, we investigated the protein-protein interaction between rOAT1 and Cav-1. METHODS: The expressions of rOAT1 and Cav-1 (mRNA and protein) were evaluated using RT-PCR and Western blot analysis. The localization of rOAT1 and Cav-1 was determined in the caveolae-rich membrane fraction isolated by sucrose density gradient ultra-centrifugation. For the direct binding between the rOAT1 and Cav-1 proteins, the immuno-precipitation method and confocal microscopy were employed. To perform functional analysis, a Xenopus oocytes expression system with the antisense oligonucleotides (ODN) technique was used. RESULTS: The expressions of rOAT1 and Cav-1 were detected in the kidney. The caveolae-rich membranous fractions from the kidney contained both rOAT1 and Cav-1 in the same fractions. The immuno-precipitation experiments showed the formation of a complex between the rOAT1 and Cav-1. The confocal microscopy using primary cultured renal proximal epithelial cells also supported the co-localization of rOAT1 and Cav-1 at the plasma membrane. The uptake function of rOAT1, as assessed by using a Xenopus oocytes expression system, was inhibited by the Xenopus Cav-1 antisense ODN. CONCLUSION: rOAT1 co-localizes with caveolin-1 in the caveolae, and caveolin-1 plays an important role in regulating the function of rOAT1.
Subject(s)
Animals , Humans , Rats , Avena , Blotting, Western , Caveolae , Caveolin 1 , Cell Membrane , Epithelial Cells , Ketoglutaric Acids , Kidney , Kidney Tubules, Proximal , Membranes , Microscopy, Confocal , Oligonucleotides, Antisense , Oocytes , Organic Anion Transporters , Protein Isoforms , Proteins , Sucrose , XenopusABSTRACT
BACKGROUND: Insulin resistance syndrome shows extreme insulin resistance and is associated with acanthosis nigricans. We can differentiate it into type A insulin resistance that has insulin receptor defect, and type B insulin resistance due to insulin receptor autoantibody. Type B insulin resistance was firstly described by Kahn in 1976. It was often found in adult female and showed autoimmune characteristics. As clinical characteristics, there are hyperglycemia, hypoglycemia, hyperinsulinemia, extreme insulin resistance and acanthosis nigricans. METHODS: We investigated 17 insulin receptor autoantibody positive cases and 8 cases of normal control who had visited Wonju Christian Hospital from October 1994 to December 1995. Among insulin receptor autoantibody positive subject, male was 4 cases and female 13 cases. Their mean age was 42.2. We compared patients who had insulin receptor antibody positive acanthosis nigricans(IRA) with normal controls. IRA patients were 6 cases(35.3%) of nomal glucose tolerance, 11 cases(64.7%) of abnormal glucose tolerance including overt diabetes mellitus. RESULTS: The 11 cases(64.7%) among IRA patrents were obese and 13 cases(76.5%) had hyperininsulinemia. In IRA patients, mean serum insulin concentration during oral glucose tolerance test was 202.1mU/mL and it was greater than 46.3 of normal controls. Insulin sensitivity in 1.79mg/L * mM * xmU * min normal controls was higher than 0.74mg/L * mM * min of IRA patients. CONCLUSION: IRA patients showed abnormal glucose tolerance including overt diabetes millitus, severe insulin resistance, hyperinsulinemia and obesity.
Subject(s)
Adult , Female , Humans , Male , Acanthosis Nigricans , Diabetes Mellitus , Glucose , Glucose Tolerance Test , Hyperglycemia , Hyperinsulinism , Hypoglycemia , Insulin Resistance , Insulin , Obesity , Receptor, InsulinABSTRACT
Thymoma has been associated with a variety of diseases, including myasthenia gravis, pure red cell aplasia (PRCA), hypogammaglobulinemia, and other abnormal immune and endocrine disorders. Herein we report a case of PRCA associated with invasive thymoma in a 65-year-old man. In spite of total thymectomy and irradiation to the mediastinum, no significant response was observed. The mechanisms and management of PRCA associated with invasive thymoma are reviewed.
Subject(s)
Aged , Humans , Agammaglobulinemia , Mediastinum , Myasthenia Gravis , Red-Cell Aplasia, Pure , Thymectomy , ThymomaABSTRACT
Carney Complex is an autosomal dominant syndrome characterized by multiple neoplasias, including myxomas at various sites and endocrine tumors, spotty pigmentations and schwannomas. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: 1) cardiac myxoma, 2) cutaneous myxoma, 3) mammary myxoma, 4) spotty mucocutaneous pigmentation, 5) primary pigmented nodular adrenal cortical disease (Cushing's syndrome), 6) testicular tumors (sexual precocity), 7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). It is thought that the genetic defects which are responsible for Carney complex maps to the short arm of chromosome 2 (2p16). There are about 200 patients with Carney complex reported in the world. We encounted a patient who had a cardiac myxoma with a family history of cardiac myxoma, acromegaly, lentigosis, testicular mass with calcification and left adrenal nodule. This patient met the criteria for the diagnosis of the complex. Therefore, we think this patient represents clinical presentation of the Carney complex and we report this case with reviews of the literatures.