A Novel Function of Apolipoprotein E: Upregulation of ATP-Binding Cassette Transporter A1 Expression

Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression

Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

<p>Abstract</p> <p>Background</p> <p><it>NDRG</it>2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that <it>NDRG</it>2 expressed differentially in normal and cancer tissues. Specifically, <it>NDRG</it>2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of <it>NDRG</it>2 inhibited the proliferation of cancer cells. <it>NDRG</it>2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether <it>NDRG</it>2 participates in carcinogenesis of the thyroid.</p> <p>Methods</p> <p>In this study, we investigated the expression profile of human <it>NDRG</it>2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc.</p> <p>Results</p> <p>The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of <it>NDRG</it>2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of <it>NDRG</it>2 expression with gender, age, different histotypes of thyroid cancers or distant metastases.</p> <p>Conclusion</p> <p>Our data indicates that <it>NDRG</it>2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of <it>NDRG2 </it>in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of <it>NDRG</it>2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.</p

The Role of crumbs Genes in the Vertebrate Cornea

crumbs genes play a role in the differentiation of the vertebrate cornea. Corneal defects associated with crumbs gene mutations are found in zebrafish mutants and human carriers of CRB1 gene mutations

The Role of crumbs Genes in the Vertebrate Cornea

crumbs genes play a role in the differentiation of the vertebrate cornea. Corneal defects associated with crumbs gene mutations are found in zebrafish mutants and human carriers of CRB1 gene mutations

Elevated Albumin in Retinas of Monkeys with Experimental Glaucoma

Albumin, a major antioxidant in the body, is increased in the retina of monkey eyes with experimental glaucoma and the increase is positively correlated with severity of glaucoma damage. The increased intracellular albumin may contribute to the survival of injured neurons in the glaucomatous retina