The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. T...The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.展开更多
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
目的综述B类I型清道夫受体(scavenger receptor class B type I,SR-BI)基因表达上调剂的研究进展。方法查阅近年来国内外相关文献29篇,对其进行归纳总结和分析。结果 SR-BI是高密度脂蛋白(high density lipoprotein,HDL)受体,能选择性...目的综述B类I型清道夫受体(scavenger receptor class B type I,SR-BI)基因表达上调剂的研究进展。方法查阅近年来国内外相关文献29篇,对其进行归纳总结和分析。结果 SR-BI是高密度脂蛋白(high density lipoprotein,HDL)受体,能选择性介导胆固醇和HDL颗粒中胆固醇酯的吸收,在HDL的代谢中起重要作用。提高SR-BI基因表达,可促进胆固醇外流,降低血浆胆固醇水平,因此SR-BI基因表达上调剂有望成为新型抗动脉粥样硬化药物。许多报道的天然或合成小分子化合物具有SR-BI基因表达上调活性,有进一步研究价值。结论已报道的化合物虽然活性值不高,直接作为SR-BI基因表达上调剂候选药物应用较为困难,但以其为先导化合物,进行结构优化,对发现新的结构新颖、活性显著的SR-BI基因表达上调剂有重要意义。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
目的探讨法尼酯X受体(farnesoid X receptor,FXR)在肝细胞中对B类清道夫受体I(scavenger receptor class B type I,SR-BI)表达的影响及可能机制。方法用FXR的特异性激动剂GW4064刺激胚胎肝细胞L02,经RT-PCR检测FXR特异性靶基因SHP(small...目的探讨法尼酯X受体(farnesoid X receptor,FXR)在肝细胞中对B类清道夫受体I(scavenger receptor class B type I,SR-BI)表达的影响及可能机制。方法用FXR的特异性激动剂GW4064刺激胚胎肝细胞L02,经RT-PCR检测FXR特异性靶基因SHP(small heterodimer partner)mRNA的表达;经RT-PCR、荧光实时定量PCR和Western blot检测SR-BI的表达;在线分析、预测SR-BI基因启动子区中FXR的可能结合位点;最后经RT-PCR检测FXR的靶基因PPARγ(过氧化物酶体增殖物激活受体γ)mRNA的表达。结果FXR的特异性配体GW4064作用于L02细胞后,SHP mRNA表达明显上调,表明FXR在L02细胞中具有功能活性。FXR活化后可在转录和翻译水平上调SR-BI的表达,同时上调PPARγ的表达。经在线分析,未在SR-BI启动子区域找到FXR的经典结合位点。结论FXR在肝细胞中可上调SR-BI的表达,其机制可能与上调PPARγ有关。展开更多
目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)...目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)表达的影响,探讨姜黄素在阿尔茨海默病(Alzheimer’s disease,AD)防治中的机制。方法:将10只6月龄的APPswe/PSEN1dE9双转基因小鼠随机分为对照组和姜黄素饲喂组,每组5只。姜黄素饲喂组每天饲喂500 ppm姜黄素,6个月后采用免疫组化法检测小鼠海马神经元SR-BⅠ和ABCA1表达的变化。结果:与对照组相比,姜黄素饲喂组小鼠海马神经元ABCA1表达明显增加(t=-10.805,P=0.000),但2组小鼠海马神经元中均未见SR-BⅠ表达。结论:姜黄素能提高APPswe/PSEN1dE9双转基因小鼠海马神经元ABCA1的表达,而SR-BⅠ在神经元中未见表达。展开更多
文摘The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.
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.
文摘目的综述B类I型清道夫受体(scavenger receptor class B type I,SR-BI)基因表达上调剂的研究进展。方法查阅近年来国内外相关文献29篇,对其进行归纳总结和分析。结果 SR-BI是高密度脂蛋白(high density lipoprotein,HDL)受体,能选择性介导胆固醇和HDL颗粒中胆固醇酯的吸收,在HDL的代谢中起重要作用。提高SR-BI基因表达,可促进胆固醇外流,降低血浆胆固醇水平,因此SR-BI基因表达上调剂有望成为新型抗动脉粥样硬化药物。许多报道的天然或合成小分子化合物具有SR-BI基因表达上调活性,有进一步研究价值。结论已报道的化合物虽然活性值不高,直接作为SR-BI基因表达上调剂候选药物应用较为困难,但以其为先导化合物,进行结构优化,对发现新的结构新颖、活性显著的SR-BI基因表达上调剂有重要意义。
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。
文摘目的探讨法尼酯X受体(farnesoid X receptor,FXR)在肝细胞中对B类清道夫受体I(scavenger receptor class B type I,SR-BI)表达的影响及可能机制。方法用FXR的特异性激动剂GW4064刺激胚胎肝细胞L02,经RT-PCR检测FXR特异性靶基因SHP(small heterodimer partner)mRNA的表达;经RT-PCR、荧光实时定量PCR和Western blot检测SR-BI的表达;在线分析、预测SR-BI基因启动子区中FXR的可能结合位点;最后经RT-PCR检测FXR的靶基因PPARγ(过氧化物酶体增殖物激活受体γ)mRNA的表达。结果FXR的特异性配体GW4064作用于L02细胞后,SHP mRNA表达明显上调,表明FXR在L02细胞中具有功能活性。FXR活化后可在转录和翻译水平上调SR-BI的表达,同时上调PPARγ的表达。经在线分析,未在SR-BI启动子区域找到FXR的经典结合位点。结论FXR在肝细胞中可上调SR-BI的表达,其机制可能与上调PPARγ有关。
文摘目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)表达的影响,探讨姜黄素在阿尔茨海默病(Alzheimer’s disease,AD)防治中的机制。方法:将10只6月龄的APPswe/PSEN1dE9双转基因小鼠随机分为对照组和姜黄素饲喂组,每组5只。姜黄素饲喂组每天饲喂500 ppm姜黄素,6个月后采用免疫组化法检测小鼠海马神经元SR-BⅠ和ABCA1表达的变化。结果:与对照组相比,姜黄素饲喂组小鼠海马神经元ABCA1表达明显增加(t=-10.805,P=0.000),但2组小鼠海马神经元中均未见SR-BⅠ表达。结论:姜黄素能提高APPswe/PSEN1dE9双转基因小鼠海马神经元ABCA1的表达,而SR-BⅠ在神经元中未见表达。
