Wu X, Wang K
Institute of Basic Medical Sciences, CAMS & PUMC, Beijing.
Chin Med Sci J. 1994 Jun;9(2):81-6.
It had been found that Beijing ducks (BD) have a high level of HDL (70%), high LCAT but very low CETP activity and will not develop atherosclerosis on an atherogenic diet, suggesting that cholesterol ester is mainly carried by HDL and metabolized through an HDL receptor pathway in the liver. However, evidence of this receptor's existence in the liver is not yet complete. In this paper, the HDL receptor in BD liver has been studied. Our experiments showed: 1) ApoE-free 125I-HDL could bind specifically to duck hepatic cell membrane with high affinity (Kd = 9.6 micrograms/ml) and was saturable (Bmax = 8.9 micrograms/mg cell membrane protein) at room temperature. 2) Competitive inhibition studies with unlabelled duck, human, rat and chick HDL and duck apo AI and its liposomes formed with PC or DMPC could inhibit the binding of 125I-HDL to duck hepatic cell membranes, but LDL, apo E and their liposomes with PC or DMPC could not with the exception of duck LDL. 3) The receptor could recognize apo AI but not apo B or E. 4) Both phosphorylase A2 and pronase could inhibit the binding activity. The above results give strong evidence for the existence of a specific HDL receptor pathway in the duck liver, supporting our hypothesis that CE in Beijing ducks is metabolized directly through the hepatic HDL receptor instead of being transferred back to VLDL and LDL, then through the LDL receptor pathway. This unique way of metabolizing CE may be behind the Beijing duck's antiatherogenicity.
已发现北京鸭(BD)具有高水平的高密度脂蛋白(HDL,70%)、高卵磷脂胆固醇酰基转移酶(LCAT)但极低的胆固醇酯转运蛋白(CETP)活性,并且在致动脉粥样化饮食条件下不会发生动脉粥样硬化,这表明胆固醇酯主要由HDL携带并通过肝脏中的HDL受体途径进行代谢。然而,该受体在肝脏中存在的证据尚不完整。在本文中,对北京鸭肝脏中的HDL受体进行了研究。我们的实验表明:1)无载脂蛋白E(ApoE)的125I-HDL能在室温下以高亲和力(解离常数Kd = 9.6微克/毫升)特异性结合鸭肝细胞膜,且具有饱和性(最大结合量Bmax = 8.9微克/毫克细胞膜蛋白)。2)用未标记的鸭、人、大鼠和鸡的HDL以及鸭载脂蛋白AI及其与磷脂酰胆碱(PC)或二肉豆蔻酰磷脂酰胆碱(DMPC)形成的脂质体进行竞争抑制研究,可抑制125I-HDL与鸭肝细胞膜的结合,但低密度脂蛋白(LDL)、载脂蛋白E及其与PC或DMPC形成的脂质体除鸭LDL外均无此作用。3)该受体能识别载脂蛋白AI,但不能识别载脂蛋白B或E。4)磷酸化酶A2和链霉蛋白酶均可抑制结合活性。上述结果为鸭肝脏中存在特异性HDL受体途径提供了有力证据,支持了我们的假说,即北京鸭中的胆固醇酯直接通过肝脏HDL受体进行代谢,而不是先转移回极低密度脂蛋白(VLDL)和低密度脂蛋白,然后通过LDL受体途径代谢。这种独特的胆固醇酯代谢方式可能是北京鸭抗动脉粥样硬化的原因。