論文 - 詳細
| RRC ID | 67925 |
|---|---|
| 著者 | Terao Y, Ayaori M, Ogura M, Yakushiji E, Uto-Kondo H, Hisada T, Ozasa H, Takiguchi S, Nakaya K, Sasaki M, Komatsu T, Iizuka M, Horii S, Mochizuki S, Yoshimura M, Ikewaki K. |
| タイトル | Effect of sulfonylurea agents on reverse cholesterol transport in vitro and vivo. |
| ジャーナル | J Atheroscler Thromb |
| Abstract |
AIM:Reverse cholesterol transport (RCT) is a critical mechanism for the anti-atherogenic property of HDL. The inhibitory effect of the sulfonylurea agent (SUA) glibenclamide on ATP binding-cassette transporter (ABC) A1 may decrease HDL function but it remains unclear whether it attenuates RCT in vivo. We therefore investigated how the SUAs glibenclamide and glimepiride affected the functionality of ABCA1/ABCG1 and scavenger receptor class B type I (SR-BI) expression in macrophages in vitro and overall RCT in vivo. METHODS:RAW264.7, HEK293 and BHK-21 cells were used for in vitro studies. To investigate RCT in vivo, 3H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were injected into mice. RESULTS:High dose (500µM) of glibenclamide inhibited ABCA1 function and apolipoprotein A-I (apoA-I)-mediated cholesterol efflux, and attenuated ABCA1 expression. Although glimepiride maintained apoA-I-mediated cholesterol efflux from RAW264.7 cells, like glibenclamide, it inhibited ABCA1-mediated cholesterol efflux from transfected HEK293 cells. Similarly, the SUAs inhibited SR-BI-mediated cholesterol efflux from transfected BHK-21 cells. High doses of SUAs increased ABCG1 expression in RAW264.7 cells, promoting HDL-mediated cholesterol efflux in an ABCG1-independent manner. Low doses (0.1-100 µM) of SUAs did not affect cholesterol efflux from macrophages despite dose-dependent increases in ABCA1/G1 expression. Furthermore, they did not change RCT or plasma lipid levels in mice. CONCLUSION:High doses of SUAs inhibited the functionality of ABCA1/SR-BI, but not ABCG1. At lower doses, they had no unfavorable effects on cholesterol efflux or overall RCT in vivo. These results indicate that SUAs do not have adverse effects on atherosclerosis contrary to previous findings for glibenclamide. |
| 巻・号 | 18(6) |
| ページ | 513-30 |
| 公開日 | 2011-1-1 |
| DOI | 10.5551/jat.7641 |
| PII | JST.JSTAGE/jat/7641 |
| PMID | 21636950 |
| MeSH | ATP-Binding Cassette Transporters / antagonists & inhibitors ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Animals Biological Transport Blotting, Western Cells, Cultured Cholesterol / metabolism* Cricetinae Glyburide / pharmacology* HEK293 Cells Humans Hypoglycemic Agents / pharmacology* In Vitro Techniques Liver / cytology Liver / drug effects Liver / metabolism Macrophages / cytology Macrophages / drug effects Macrophages / metabolism Macrophages, Peritoneal / cytology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / metabolism Male Mice Mice, Inbred C57BL RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Scavenger Receptors, Class B / antagonists & inhibitors Scavenger Receptors, Class B / genetics Scavenger Receptors, Class B / metabolism* |
| IF | 3.876 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) COS-7(RCB0539) 293(RCB1637) BHK-21 |