Division of Endocrinology & Metabolism and Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-Cho, Kita-gun, Kagawa, 761-0793, Japan.
Ann Med. 2010 Mar;42(2):151-60. doi: 10.3109/07853891003601556.
A scavenger receptor of the B class (SR-BI)/human homolog of SR-BI, CD36, and LIMP II analogous-1 (CLA-1), has been identified as a receptor for high-density lipoprotein (HDL). Mice lacking SR-B1 develop anemia, plausibly explained by the observation that the erythrocyte life-span in these animals is reduced. Erythropoietin (EPO) is known to promote survival of erythroid cells, in large part through protection from apoptosis. We have examined the role of EPO on hSR-BI/CLA-1 expression and erythrocyte apoptosis. Endogenous expression of hSR-BI/CLA-1 was increased by exposure to EPO. EPO increased transcriptional activity of hSR-BI/CLA-1 promoter. The stimulatory effect of EPO on hSR-BI/CLA-1 promoter activity was abrogated by LY294002, specific inhibitor of phosphatidylinositol-3 kinase (PI3K). Constitutively active Akt stimulates the activity of the hSR-BI/CLA-1 promoter and a dominant-negative mutant of Akt abolished the ability of EPO to stimulate promoter activity. Finally, EPO in combination with HDL protected the cell from apoptosis, which suggests that hSR-BI/CLA-1 induced by EPO might contribute to the erythrocyte life-span.
B 类清道夫受体（SR-BI）/SR-BI 的人同源物、CD36 和 LIMP II 类似物-1（CLA-1）已被鉴定为高密度脂蛋白（HDL）的受体。缺乏 SR-B1 的小鼠会出现贫血，这可以通过观察到这些动物的红细胞寿命缩短来解释。促红细胞生成素（EPO）已知可通过防止细胞凋亡来促进红细胞的存活。我们研究了 EPO 对 hSR-BI/CLA-1 表达和红细胞凋亡的作用。EPO 可增加内源性 hSR-BI/CLA-1 的表达。EPO 增加了 hSR-BI/CLA-1 启动子的转录活性。EPO 对 hSR-BI/CLA-1 启动子活性的刺激作用被磷脂酰肌醇-3 激酶（PI3K）的特异性抑制剂 LY294002 阻断。组成性激活的 Akt 可刺激 hSR-BI/CLA-1 启动子的活性，而 Akt 的显性失活突变则消除了 EPO 刺激启动子活性的能力。最后，EPO 与 HDL 联合使用可保护细胞免于凋亡，这表明 EPO 诱导的 hSR-BI/CLA-1 可能有助于延长红细胞的寿命。
