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Journal Article 
Paraoxon Down Regulates ATP-binding Cassette Transporter A1 Expression and Decreases Cholesterol Efflux Through Cyclic AMP Signaling Pathway in RAW 264.7 Macrophage-derived Foam Cells 
Zhou Shou-Hong; Yang Xu-Hong; Wu Shu-Jin; Chen Geng-Rong; Liu Li-Ying 
Shengwu Huaxue yu Shengwu Wuli Jinzhan / Progress in Biochemistry and Biophysics
ISSN: 1000-3282 
ATP-binding Cassette Transporter A I (ABCA I) plays a critical role in the reverse cholesterol transport (RCT) Previous studies showed that paraoxon, the active metabolite of organophosphorus insecticide, increased cholesterol retention in macrophages However, its underlying mechanisms remain to be elucidated The effect of paraoxon on ABCA I expression and ABCA I-dependent cholesterol efflux was investigated, and then the role of cyclic adenosine monophospate (cAMP) signaling pathway in the regulation of ABCA I expression and ABCA I-mediated cholesterol efflux was examined by paraoxon, in RAW 264 7 macrophage-derived foam cells Results showed that paraoxon significantly down regulated ABCA I expression and reduced ABCA I-dependent cholesterol efflux and increased the levels of the total, free and esterified cholesterols in a time- and dose-dependent manner Paraoxon also markedly reduced cAMP level and decreased adenylate cyclase (AC) activity and increased cAMP-specific phosphodicsterase (PDE) activity Furthermore, cAMP analogs dibutyryl cyclic adenosine monophosphate (dBcAMP) markedly compensated the down-regulation of ABCAI expression and partly compensated the reduction of ABCAI-mcdiated cholesterol efflux induced by paraoxon. Also, both adenylate cyclase agonist forskolin and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) markedly compensated the suppression effect on cAMP level induced by paraoxon In conclusion, the results mentioned above suggest that paraoxon down regulates ABCA I expression and decreases ABCAI-mediated cholesterol efflux through cyclic AMP signaling pathway in RAW 264.7 macrophage-derived foam cells 
paraoxon; ABCA1; cAMP; atherosclerosis; reverse cholesterol transport