Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of S...Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.展开更多
目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经...目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经乙酰化低密度脂蛋白(ac-LDL)及3H-胆固醇处理过的小鼠巨噬细胞悬液(0.5 m L/鼠,细胞数达5.0×106),单独笼养24 h后取血,酶法测定血脂;测定血清、肝脏和粪便中的3H-胆固醇含量(占注射总量的百分比);逆转录聚合酶链反应测定小鼠肝脏SR-B1 m RNA表达。结果与对照组比较,苯扎贝特组小鼠肝脏SR-B1 m RNA表达水平增高,粪便中的胆固醇流出率增加。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组血清3H-胆固醇含量较对照组显著增加,分别增加100%、131%和110%。不同剂量苯扎贝特(0.10%、0.25%、0.50%W/W)干预组小鼠肝脏3H-胆固醇含量较对照组显著增加,分别增加86.4%、52.3%和51.6%。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组小鼠粪便3H-胆固醇含量较对照组显著增加,分别增加为110%、140%和160%。结论苯扎贝特能上调肝脏SR-B1 m RNA表达,促进体内胆固醇逆转运,加速胆固醇由粪便清除,利于动脉粥样硬化的防治。展开更多
丙型肝炎病毒(hepatitis C virus,HCV)入侵宿主细胞是由多种受体分子介导的多步骤过程,其中B族Ⅰ型清道夫受体(SR-BⅠ/SCARB1)被认为是最先与HCV作用的受体。SR-BⅠ能够与HCV包膜糖蛋白E2相结合,在此过程中位于E2蛋白氨基末端的高变区1(...丙型肝炎病毒(hepatitis C virus,HCV)入侵宿主细胞是由多种受体分子介导的多步骤过程,其中B族Ⅰ型清道夫受体(SR-BⅠ/SCARB1)被认为是最先与HCV作用的受体。SR-BⅠ能够与HCV包膜糖蛋白E2相结合,在此过程中位于E2蛋白氨基末端的高变区1(hypervariable region 1,HVR1)起关键作用。SR-BⅠ与HCV的相互作用不仅能够介导HCV的细胞入侵,还能降低抗体对HCV的中和作用,有助于HCV的免疫逃避。因此,深入研究SR-BⅠ在HCV入侵细胞过程中的作用机制,有望发现在HCV感染的初始环节能够高效地阻断HCV入侵细胞的靶分子,从而预防和治疗HCV的感染。本文就SR-BⅠ的生物学特性、SR-BⅠ与HCV的相互作用对病毒入侵细胞的影响及机制等方面的最新进展作一综述。展开更多
基金Supported by Top Institute Pharma (TIPharma Project T2-110 Hoekstra M and Van Berkel TJC)+2 种基金Grant 2008T070 from the Netherlands Heart Foundation (Hoekstra M)VIDI Grant 917.66.301 from the Netherlands Organization for Scientific Research (Van Eck M)Van Eck Mis an Established Investigator of the Netherlands Heart Foundation (Grant 2007T056)
文摘Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.
文摘目的探讨苯扎贝特干预后小鼠肝脏B族I型清道夫受体(SR-B1)m RNA变化及对小鼠体内胆固醇逆转运的影响。方法 28只C57BL/6小鼠随机分为4组,分别给予普通饲料、不同剂量的苯扎贝特(0.10%、0.25%、0.50%)添加普通饲料喂养4周后,腹腔注射经乙酰化低密度脂蛋白(ac-LDL)及3H-胆固醇处理过的小鼠巨噬细胞悬液(0.5 m L/鼠,细胞数达5.0×106),单独笼养24 h后取血,酶法测定血脂;测定血清、肝脏和粪便中的3H-胆固醇含量(占注射总量的百分比);逆转录聚合酶链反应测定小鼠肝脏SR-B1 m RNA表达。结果与对照组比较,苯扎贝特组小鼠肝脏SR-B1 m RNA表达水平增高,粪便中的胆固醇流出率增加。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组血清3H-胆固醇含量较对照组显著增加,分别增加100%、131%和110%。不同剂量苯扎贝特(0.10%、0.25%、0.50%W/W)干预组小鼠肝脏3H-胆固醇含量较对照组显著增加,分别增加86.4%、52.3%和51.6%。不同剂量苯扎贝特(0.10%、0.25%、0.50%)干预组小鼠粪便3H-胆固醇含量较对照组显著增加,分别增加为110%、140%和160%。结论苯扎贝特能上调肝脏SR-B1 m RNA表达,促进体内胆固醇逆转运,加速胆固醇由粪便清除,利于动脉粥样硬化的防治。
文摘丙型肝炎病毒(hepatitis C virus,HCV)入侵宿主细胞是由多种受体分子介导的多步骤过程,其中B族Ⅰ型清道夫受体(SR-BⅠ/SCARB1)被认为是最先与HCV作用的受体。SR-BⅠ能够与HCV包膜糖蛋白E2相结合,在此过程中位于E2蛋白氨基末端的高变区1(hypervariable region 1,HVR1)起关键作用。SR-BⅠ与HCV的相互作用不仅能够介导HCV的细胞入侵,还能降低抗体对HCV的中和作用,有助于HCV的免疫逃避。因此,深入研究SR-BⅠ在HCV入侵细胞过程中的作用机制,有望发现在HCV感染的初始环节能够高效地阻断HCV入侵细胞的靶分子,从而预防和治疗HCV的感染。本文就SR-BⅠ的生物学特性、SR-BⅠ与HCV的相互作用对病毒入侵细胞的影响及机制等方面的最新进展作一综述。
