Ethanol Augments PDGF-Induced NADPH Oxidase Activity and Proliferation in Rat Pancreatic Stellate Cells |
| |
| Institution: | 1. Department of Veterans Affairs/University of California, Los Angeles/Research Center for Alcoholic Liver and Pancreatic Diseases, Los Angeles, Calif., USA;;2. Liverpool Hospital and the University of New South Wales,, Los Angeles, Calif., USA; Sydney, Australia;1. Department of Geology, Ferdowsi University of Mashhad, Iran;2. Department of Economic Geology, Tarbiat Modares University, Tehran, Iran;3. Department of Lithospheric Science, Geochronology Laboratory, University of Wien, Austria;4. Department of Geosciences, Geobiotec Research Unit, University of Aveiro, Portugal;1. Cardiology Service, Brooke Army Medical Center, MCHE-MDC, 3551 Roger Brooke Drive, San Antonio, TX 78234-6200, USA;2. Noninvasive Cardiovascular Imaging Program, Cardiovascular Division, Department of Medicine, Brigham and Women''s Hospital, Boston, MA, USA;3. Department of Radiology, Brigham and Women''s Hospital, Boston, MA, USA;4. Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, FL, USA;1. Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture/Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, P.R. China;2. College of Resources and Environment, South China Agricultural University, Guangzhou 510642, P.R. China;1. Centro Interdisciplinario de Ciencias Marinas, Instituto Politécnico Nacional, Av. IPN s/n, C.P. 23090 La Paz, B. C. S., Mexico;2. Centro Regional de Investigación Pesquera-Instituto Nacional de Pesca, Carretera A Pichilingue Km1, s/n, Col. Esterito, C.P. 23020 La Paz, B. C. S., Mexico;3. Centro de Investigaciones Biológicas del Noroeste CIBNOR, Unidad Sonora, Campus Guaymas. Km. 2.35 Camino al Tular Estero de Bacochibampo, C.P. 85465 Guaymas, Sonora, Mexico;1. Department of Microbiology (VM), Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Department of Microbiology (FH, SS, SJ), Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India |
| |
| Abstract: | Background/Aims: Activated stellate cells are considered the principal mediators of chronic alcoholic pancreatitis/fibrosis. However the mechanisms of alcohol action on pancreatic stellate cells (PaSCs) are poorly understood. The aims of this study were to determine the presence and role of the NADPH oxidase system in mediating alcohol effects on PaSCs with specific emphasis on proliferation. Methods: PaSC NADPH oxidase components mRNA and protein were determined by RT-PCR and Western blot. The NADPH oxidase activity was measured by detecting the production of reactive oxygen species using lucigenin-derived chemiluminescence assay. PaSC DNA synthesis, a measure of proliferation, was performed by determining the 3H] thymidine incorporation into DNA. Results: mRNA for NADPH oxidase components Nox1, gp91phox, Nox4, p22Pphoxhox, p47phox and p67phox and protein for NADPH oxidase subunits gp91phox, p22phox, p47phox and p67phox are present in PaSCs. Treatment with platelet-derived growth factor (PDGF) significantly increased the NADPH oxidase activity and DNA synthesis in cultured PaSCs. Alcohol treatment markedly augmented both the NADPH oxidase activity and the DNA synthesis caused by PDGF, which was prevented byantioxidant N-ace-tyl-l-cysteine, ROS scavenger tiron, and the NADPH oxidase inhibitor diphenyleneiodium.Theeffectsof PDGF on NADPH oxidase activity and DNA synthesis were prevented in PaSCs isolated from the pancreas of mice with a genetic deficiency of p47phox. Conclusions: Ethanol causes proliferation of stellate cells by augmenting the activation of the cell's NADPH oxidase system stimulated by PDGF. These results provide new insights into the mechanisms of alcohol-induced fibrosing disorders. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
