University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Proteomic identification of nitrated proteins in Alzheimer's disease brain.

Abstract: Nitration of tyrosine in biological conditions represents a pathological event that is associated with several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease and Alzheimer’s disease (AD). Increased levels of nitrated proteins have been reported in AD brain and CSF, demonstrating the potential involvement of reactive nitrogen species (RNS) in neurodegeneration associated with this disease. Reaction of NO with O � : 2 leads to formation of peroxynitrite ONOO – , which following protonation, generates cytotoxic species that oxidize and nitrate proteins. Several findings suggest an important role of protein nitration in modulating the activity of key enzymes in neurodegenerative disorders, although extensive studies on specific targets of protein nitration in disease are still missing. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. We previously applied a proteomics approach to determine specific targets of protein oxidation in AD brain, by successfully coupling immunochemical detection of protein carbonyls with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry analysis. In the present study, we extend our investigation of protein oxidative modification in AD brain to targets of protein nitration. The identification of six targets of protein nitration in AD brain provides evidence to the importance of oxidative stress in the progression of this dementing disease and

MicroRNAs in NF-κB signaling

Abstract: Nuclear factor kB (NF-kB) is a transcriptional factor that regulates a battery of genes that are critical to innate and adaptive immunity, cell proliferation, inflammation, and tumor development. MicroRNAs (miRNAs) are short RNA molecules of 20‐25 nucleotides in length that negatively regulate gene expression in animals and plants primarily by targeting 3 ′ untranslated regions of mRNAs. In this work, we review the convergence of miRNAs and NF-kB signaling and dysregulation of miRNAs and NF-kB activation in human diseases, particularly in cancer. The function of miR-146, miR-155, miR-181b, miR-21, and miR-301a in NF-kB activation and their impact on tumorigenesis are discussed. Given that over 1000 human miRNAs have been identified, rendering miRNAs one of the most abundant classes of regulatory molecules, deciphering their biological function and pathological contribution in NF-kB dysregulation is essential to appreciate the complexity of immune systems and to develop therapeutics against cancer.

Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants

Abstract: Background Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. Methods We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. Results Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variant...

Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta.

Abstract: Epidemiological evidence indicates that phytoestrogens inhibit cancer formation and growth, reduce cholesterol levels, and show benefits in treating osteoporosis. At least some of these activities are mediated through the interaction of phytoestrogens with estrogen receptors a and b (ERa and ERb). Resveratrol, trans-3,5,49-trihydroxystilbene, is a phytoestrogen in grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic extracts from MCF-7 and rat uteri. However, the contribution of ERa vs. ERb in this binding is unknown. Here we report that resveratrol binds ERb and ERa with comparable affinity, but with 7,000-fold lower affinity than estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind ERb with higher affinity than ERa. Resveratrol acts as an estrogen agonist and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing either ERa or ERb. The estrogen agonist activity of resveratrol depends on the ERE sequence and the type of ER. Resveratrol-liganded ERb has higher transcriptional activity than E2-liganded ERb at a single palindromic ERE. This indicates that those tissues that uniquely express ERb or that express higher levels of ERb than ERa may be more sensitive to resveratrol’s estrogen agonist activity. For the natural, imperfect EREs from the human c-fos, pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable to that induced by E2. We report that resveratrol exhibits E2 antagonist activity for ERa with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERb. These data indicate that resveratrol differentially affects the transcriptional activity of ERa and ERb in an ERE sequence-dependent manner. (Endocrinology 141: 3657‐3667, 2000)