Osaka University

About: Osaka University is a education organization based out in Osaka, Japan. It is known for research contribution in the topics: Laser & Catalysis. The organization has 83778 authors who have published 185669 publications receiving 5158122 citations. The organization is also known as: Ōsaka daigaku.

Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy

Abstract: G-protein-coupled receptor (GPCR) agonists are well-known inducers of cardiac hypertrophy. We found that the shedding of heparin-binding epidermal growth factor (HB-EGF) resulting from metalloproteinase activation and subsequent transactivation of the epidermal growth factor receptor occurred when cardiomyocytes were stimulated by GPCR agonists, leading to cardiac hypertrophy. A new inhibitor of HB-EGF shedding, KB-R7785, blocked this signaling. We cloned a disintegrin and metalloprotease 12 (ADAM12) as a specific enzyme to shed HB-EGF in the heart and found that dominant-negative expression of ADAM12 abrogated this signaling. KB-R7785 bound directly to ADAM12, suggesting that inhibition of ADAM12 blocked the shedding of HB-EGF. In mice with cardiac hypertrophy, KB-R7785 inhibited the shedding of HB-EGF and attenuated hypertrophic changes. These data suggest that shedding of HB-EGF by ADAM12 plays an important role in cardiac hypertrophy, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy.

Symbol Nomenclature for Graphical Representations of Glycans.

Abstract: Author(s): Varki, Ajit; Cummings, Richard D; Aebi, Markus; Packer, Nicole H; Seeberger, Peter H; Esko, Jeffrey D; Stanley, Pamela; Hart, Gerald; Darvill, Alan; Kinoshita, Taroh; Prestegard, James J; Schnaar, Ronald L; Freeze, Hudson H; Marth, Jamey D; Bertozzi, Carolyn R; Etzler, Marilynn E; Frank, Martin; Vliegenthart, Johannes Fg; Lutteke, Thomas; Perez, Serge; Bolton, Evan; Rudd, Pauline; Paulson, James; Kanehisa, Minoru; Toukach, Philip; Aoki-Kinoshita, Kiyoko F; Dell, Anne; Narimatsu, Hisashi; York, William; Taniguchi, Naoyuki; Kornfeld, Stuart

Induction of Adiponectin, a Fat-Derived Antidiabetic and Antiatherogenic Factor, by Nuclear Receptors

Abstract: Adiponectin is a fat-derived hormone with antidiabetic and antiatherogenic properties. Hypoadiponectinemia seen in obesity is associated with insulin-resistant diabetes and atherosclerosis. Thiazolidinediones, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, have been shown to increase plasma adiponectin levels by the transcriptional induction in adipose tissues. However, the precise mechanism of such action is unknown. In this study, we have identified a functional PPAR-responsive element (PPRE) in human adiponectin promoter. PPAR-gamma/retinoid X receptor (RXR) heterodimer directly bound to the PPRE and increased the promoter activity in cells. In adipocytes, point mutation of the PPRE markedly reduced the basal transcriptional activity and completely blocked thiazolidinedione-induced transactivation of adiponectin promoter. We have also identified a responsive element of another orphan nuclear receptor, liver receptor homolog-1 (LRH-1), in adiponectin promoter. LRH-1 was expressed in 3T3-L1 cells and rat adipocytes. LRH-1 bound specifically to the identified responsive element (LRH-RE). LRH-1 augmented PPAR-gamma-induced transactivation of adiponectin promoter, and point mutation of the LRH-RE significantly decreased the basal and thiazolidinedione-induced activities of adiponectin promoter. Our results indicate that PPAR-gamma and LRH-1 play significant roles in the transcriptional activation of adiponectin gene via the PPRE and the LRH-RE in its promoter.