%0 Journal Article
%T The Role of PPAR¦Ã in Helicobacter pylori Infection and Gastric Carcinogenesis
%A Jong-Min Lee
%A Sung Soo Kim
%A Young-Seok Cho
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/687570
%X Peroxisome proliferator-activated receptor (PPAR ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPAR plays an important role in gastric mucosal injury due to Helicobacter pylori (H. pylori). As H. pylori infection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPAR in H. pylori infection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPAR in H. pylori infection and its related gastric carcinogenesis. 1. Introduction Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. To date, three isoforms of PPARs (PPAR¦Á, PPAR¦Ä/¦Â, and PPAR¦Ã) have been identified in mammals. PPAR forms a heterodimer with its preferential binding partner¡ªretinoid X receptor (RXR). The function of PPAR/RXR heterodimer depends on its interactions with cofactor complexes (coactivators or corepressors). After activation by ligand, the PPAR/RXR heterodimer binds to specific DNA response elements called peroxisome proliferator response elements (PPREs) of the target genes. This results in transcription regulation of these genes (Figure 1) [1]. PPARs play a significant role in regulation of fatty acid oxidation and glucose utilization [2]. PPAR¦Ã was originally identified as a differentiation transcription factor for adipose tissue [3]. In addition, PPAR¦Ã is involved in the control of inflammation and glucose metabolism and participates in the processes of cellular proliferation, differentiation, and apoptosis [4]. Natural ligands for PPAR¦Ã are 15-deoxy-¦¤12,14-prostaglandin J2 (15d-PGJ2) and various polyunsaturated fatty acids [5, 6]. The insulin sensitizing thiazolinediones, which are selective ligands of the nuclear transcription factor PPAR¦Ã, were the first drugs used to treat insulin resistance in patients with type II diabetes [7]. Figure 1: A basic mechanism of PPAR signaling. Following ligand binding, PPAR forms a heterodimer with RXR, which binds to the PPRE of target genes and regulates the transcription of these genes. Helicobacter pylori (H. pylori) infection is the main etiologic agent in gastric inflammation, and longstanding infection with this organism is linked to gastric cancer [8]. Based on epidemiological studies, the risk of gastric cancer conferred by H. pylori
%U http://www.hindawi.com/journals/ppar/2012/687570/