Edna Meilin1, Michael Aviram, Tony Hayek. 1. The Lipid Research Laboratory, Technion, The Rappaport Family Institute for Research in the Medical Science, Rambam Medical Center, Haifa, Israel.
Abstract
OBJECTIVE: The present study investigates the role of paraoxonase 2 (PON2) in the attenuation of macrophage triglycerides (TG) biosynthesis, and oxidative stress, under diabetic conditions. METHODS: Peritoneal macrophages (MPM) from PON2-deficient and from C57BL/6 control mice were harvested and cultured under normal (5mM) or high glucose concentration (30mM), and evaluated for cellular TG metabolism as well as for their oxidative stress. RESULTS: In PON2-deficient MPM vs. control MPM, under diabetic conditions (high glucose concentration), we observed substantial increment in TG accumulation (3 fold), TG biosynthesis (2.6 fold) and microsomal diacylglycerol acyltransferase1 (DGAT1) activity (+60%). Furthermore, in these cells we have demonstrated increased oxidative stress, as expressed by significant increment in cellular oxidative stress (+25%), macrophage-mediated LDL oxidation (+41%) and expression of the receptor for advanced glycation end products - RAGE (+18%). Apocynin, an NADPH-oxidase inhibitor, abolished the increment in MPM TG accumulation, MPM TG biosynthesis, and microsomal DGAT1 activity, as a result of PON2-deficiency, under diabetic conditions. CONCLUSION: We conclude that PON2 has a significant protective role against macrophage triglyceride accumulation, macrophage TG biosynthesis, microsomal DGAT1 activity and macrophage oxidative stress, under high glucose concentrations. We suggest that this protective effect may be mediated by PON2 through the attenuation of NADPH-oxidase activity. The use of appropriate means to increase macrophage PON2 expression can lead to attenuation in macrophage TG accumulation and in cellular oxidative stress, under diabetic conditions, and thus may contribute to the decrement in macrophage atherogenicity and foam cell formation, attenuating the development of vascular complications in diabetes mellitus. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVE: The present study investigates the role of paraoxonase 2 (PON2) in the attenuation of macrophage triglycerides (TG) biosynthesis, and oxidative stress, under diabetic conditions. METHODS: Peritoneal macrophages (MPM) from PON2-deficient and from C57BL/6 control mice were harvested and cultured under normal (5mM) or high glucose concentration (30mM), and evaluated for cellular TG metabolism as well as for their oxidative stress. RESULTS: In PON2-deficient MPM vs. control MPM, under diabetic conditions (high glucose concentration), we observed substantial increment in TG accumulation (3 fold), TG biosynthesis (2.6 fold) and microsomal diacylglycerol acyltransferase1 (DGAT1) activity (+60%). Furthermore, in these cells we have demonstrated increased oxidative stress, as expressed by significant increment in cellular oxidative stress (+25%), macrophage-mediated LDL oxidation (+41%) and expression of the receptor for advanced glycation end products - RAGE (+18%). Apocynin, an NADPH-oxidase inhibitor, abolished the increment in MPM TG accumulation, MPM TG biosynthesis, and microsomal DGAT1 activity, as a result of PON2-deficiency, under diabetic conditions. CONCLUSION: We conclude that PON2 has a significant protective role against macrophage triglyceride accumulation, macrophage TG biosynthesis, microsomal DGAT1 activity and macrophage oxidative stress, under high glucose concentrations. We suggest that this protective effect may be mediated by PON2 through the attenuation of NADPH-oxidase activity. The use of appropriate means to increase macrophage PON2 expression can lead to attenuation in macrophage TG accumulation and in cellular oxidative stress, under diabetic conditions, and thus may contribute to the decrement in macrophage atherogenicity and foam cell formation, attenuating the development of vascular complications in diabetes mellitus. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Authors: Lucio G Costa; Rian de Laat; Khoi Dao; Claudia Pellacani; Toby B Cole; Clement E Furlong Journal: Neurotoxicology Date: 2013-09-04 Impact factor: 4.294
Authors: Aaron M Neely; Guoping Zhao; Christian Schwarzer; Nicole S Stivers; Aaron G Whitt; Shuhan Meng; Joseph A Burlison; Terry E Machen; Chi Li Journal: Cell Microbiol Date: 2017-10-09 Impact factor: 3.715
Authors: Yu Yang; Yanrong Zhang; Santiago Cuevas; Van Anthony Villar; Crisanto Escano; Laureano D Asico; Peiying Yu; David K Grandy; Robin A Felder; Ines Armando; Pedro A Jose Journal: Free Radic Biol Med Date: 2012-05-23 Impact factor: 7.376
Authors: Anastacia M Garcia; Mary L Ladage; Dennis R Dumesnil; Khadiza Zaman; Vladimir Shulaev; Rajeev K Azad; Pamela A Padilla Journal: Genetics Date: 2015-03-10 Impact factor: 4.562