Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis.

Abstract

To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes.

• Authors: Jun-ichi Satoh, Megumi Nakanishi, Fumiko Koike, Sachiko Miyake, Toshiyuki Yamamoto, Mitsuru Kawai, Seiji Kikuchi, Kyouichi Nomura, Kazumasa Yokoyama, Kohei Ota, Takashi Kanda, Toshiyuki Fukazawa, Takashi Yamamura
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 18 Issue 3 Pg. 537-50 (Apr 2005) ISSN: 0969-9961 [Print] United States
• PMID: 15755681 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Apoptosis (physiology)
• DNA Damage (genetics)
• Down-Regulation (genetics)
• Female
• Gene Expression Profiling (methods, statistics & numerical data)
• Humans
• Male
• Middle Aged
• Multiple Sclerosis (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis (methods, statistics & numerical data)
• Up-Regulation (genetics)