Mira Rosenblat1, Nina Volkova, Michael Aviram. 1. The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel.
Abstract
OBJECTIVE: To examine whether the beneficial effects of PJ consumption by mice on their macrophages are mediated via PJ-induced increment in serum paraoxonase 1 (PON1) activity and/or in macrophage PON2 expression. METHODS AND RESULTS: We performed studies in peritoneal macrophages (MPM) from C57BL/6 control mice, or from PON1KO mice, or from PON2KO mice that consumed PJ (200 microg of gallic acid equivalents/mouse/day, for 1 month period). PJ consumption by C57BL/6 mice resulted in a significant increment, by 36% in serum PON1 catalytic activities, and upregulated MPM PON2 expression. In MPM from C57BL/6 or from PON1KO mice that consumed PJ, the extent of cell-mediated LDL oxidation was decreased by 22%, and that of cellular superoxide release by 20-26%. In contrast, PJ consumption by PON2KO mice resulted in a minimal inhibitory effect on macrophage oxidative stress by only 4-9%. Unlike PJ antioxidative effects in MPM, PJ anti-atherogenic effects on MPM cholesterol and triglyceride metabolism were similar in all mice groups that consumed PJ. After PJ consumption, cellular cholesterol content was decreased by 14-19%, and this could be attributed to a significant inhibition in MPM cholesterol biosynthesis rate by 20-32%, and/or to stimulation of HDL-mediated cholesterol efflux from the cells by 22-37%. Similarly, MPM triglyceride content and triglyceride biosynthesis rate were both significantly decreased after PJ consumption, by 16-27% and by 22-28%, respectively. CONCLUSION: PJ consumption antioxidative properties on mouse macrophages, but not PJ beneficial effects on macrophage cholesterol and triglyceride metabolism, are mediated via PJ-induced stimulation of macrophage PON2 expression. Serum PON1 stimulation by PJ consumption, however, was not involved in PJ-induced effects on macrophages. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVE: To examine whether the beneficial effects of PJ consumption by mice on their macrophages are mediated via PJ-induced increment in serum paraoxonase 1 (PON1) activity and/or in macrophage PON2 expression. METHODS AND RESULTS: We performed studies in peritoneal macrophages (MPM) from C57BL/6 control mice, or from PON1KO mice, or from PON2KO mice that consumed PJ (200 microg of gallic acid equivalents/mouse/day, for 1 month period). PJ consumption by C57BL/6 mice resulted in a significant increment, by 36% in serum PON1 catalytic activities, and upregulated MPM PON2 expression. In MPM from C57BL/6 or from PON1KO mice that consumed PJ, the extent of cell-mediated LDL oxidation was decreased by 22%, and that of cellular superoxide release by 20-26%. In contrast, PJ consumption by PON2KO mice resulted in a minimal inhibitory effect on macrophage oxidative stress by only 4-9%. Unlike PJ antioxidative effects in MPM, PJ anti-atherogenic effects on MPM cholesterol and triglyceride metabolism were similar in all mice groups that consumed PJ. After PJ consumption, cellular cholesterol content was decreased by 14-19%, and this could be attributed to a significant inhibition in MPM cholesterol biosynthesis rate by 20-32%, and/or to stimulation of HDL-mediated cholesterol efflux from the cells by 22-37%. Similarly, MPM triglyceride content and triglyceride biosynthesis rate were both significantly decreased after PJ consumption, by 16-27% and by 22-28%, respectively. CONCLUSION: PJ consumption antioxidative properties on mouse macrophages, but not PJ beneficial effects on macrophage cholesterol and triglyceride metabolism, are mediated via PJ-induced stimulation of macrophage PON2 expression. Serum PON1 stimulation by PJ consumption, however, was not involved in PJ-induced effects on macrophages. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.