作者机构：
[杨云波] Department of Pharmacology, Institute of Pharmacy, Traditional Chinese Medical College, Changsha 410007, China;Inst. of Pharmacy and Pharmacology, Nanhua University, Hengyang 421001, China;[黄红林; 廖端芳; 谢志忠] Department of Pharmacology, Institute of Pharmacy, Traditional Chinese Medical College, Changsha 410007, China, Inst. of Pharmacy and Pharmacology, Nanhua University, Hengyang 421001, China
通讯机构：
[Yang, Y.-B.] D;Department of Pharmacology, Institute of Pharmacy, Traditional Chinese Medical College, China
摘要：
AIM: To identify the specific serine/threonine residues in the C-terminal tail of thromboxane receptor α (TPα)being phosphorylated and desensitized, and various alanine mutants of these serine/threonine residues were checkedfor their ability to serve as substrates. METHODS: To facilitate the identification of the intracellular domainsinvolved in phosphorylation, glutathione S-transferase (GST)-intracellular domain fusion proteins were used assubstrates for the purified PKC, and then the cDNA of phosphorylated protein was mutagenized to localize themajor site of receptor phosphorylation induced by protein kinase C. Human embryonic kidney (HEK) 293 cellsstably transfected with the His-tagged wild type or mutant TPα were used to study the phosphorylation anddesensitization. RESULTS: Only the C-terminal tail can be used as a substrate for the purified PKC. Set-331(mP4) was demonstrated to be heavily phosphorylated, Ser-324 (mP1) was shown to be slightly phosphorylated,Ser-329 was illustrated to be faintly phosphorylated, and other Ser/Thr residues were not found to be phosphorylated.Phorbol-12-myristate-13-acetate (PMA) induced receptor phosphorylation in HEK 293 cells expressing the wildtype TPα. However, PMA did not significantly trigger receptor phosphorylation in I-IEK 293 cells expressing theS331A mutant receptor. Pretreatment of the cells expressing the wild type with PMA inhibited I-BOP induced Ca~(2+) release, however, pretreatment of the cells expressing the S33 lA mutant receptor with PMA did not abolish I-BOP induced Ca~(2+) release. CONCLUSION: Ser-331 is the major and crucial site of receptor phosphorylation and desensitization.
摘要：
AIM: To investigate the mechanism by which probucol (PBC) affected adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). METHODS: Effects of PBC on expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, a nd E-selectin in human umbilical vein endothelial cells were examined. Moreover, the inhibitory effect of PBC were compared with that of monoclonal antibodies (mAbs) to ICAM-1, VCAM-1, P-selectin, and E-select in on adhesion induced by oxidized-low density lipoprotein(Ox-LDL). RESULTS: PBC at 10 to 80 micromol/L inhibited Ox-LD L-induced adhesion index from 16.7 % to 7.0 % (P < 0.01) and Ox-LDL-induced expression of ICAM-1 (75 %) and P-selectin (72 %). mAbs to ICAM -1 or P-selectin, when used alone, could only slightly reduce the adhesion of monocyte to HUVEC. When both monoclonal antibodies were used in combination, the adhesion was markedly inhibited from 16.7 % to 11.3 % (P < 0.01), but the effect was still weaker than that of PBC (average 9.3 %). CONCLUSION: PBC exerts its inhibitory effect on the adhesion of monocyte to HUVEC by inhibiting the expression of ICAM-1 and P-selectin.
摘要：
目的研究醛糖还原酶相似蛋白(aldose reductase like protein,ARL-1)在肝癌细胞中的功能及ARL-1基因高表达与肝癌耐药之间的关系.方法通过阳离子脂质体转染法将ARL-1基因导入HepG2细胞,建立稳定表达该基因的细胞株,采用MTT法检测细胞对含醛基药物的耐药变化情况.结果转染细胞与未转染细胞相比,对含醛基的抗肿瘤药物如阿霉素、丝裂霉素的耐药性明显增强,其半数抑制浓度(IC50)分别提高到2.6倍和3.1倍,ADM组t=6.39,P＜0.05,MMC组t=30.06,P＜0.01.用不含醛基的5-氟尿嘧啶处理两组细胞,则未发现有明显的耐药差异(t=0.684,P＞0.05).结论ARL-1的表达上调可能是肿瘤细胞对含醛基抗肿瘤药物耐药的主要原因之一.
作者机构：
[唐圣松; 耿以琪; 陈桂彬; 饶青; 吴克复] State Key Laboratory of Experimental Hematology, Institute Of Hematology, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, 300020, China
摘要：
AIM: To investigate the mechanism by which probucol (PBC) affected adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). METHODS: Effects of PBC on expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin in human umbilical vein endothelial cells were examined. Moreover, the inhibitory effect of PBC were compared with that of monoclonal antibodies (mAbs) to ICAM-1, VCAM-1, P-selectin, and E-selectin on adhesion induced by oxidized-low density lipoprotein (Ox-LDL). RESULTS: PBC at 10 to 80 μmol/L inhibited Ox-LDL induced adhesion index from 16.7 % to 7.0 % (P < 0.01) and Ox-LDL-induced expression of ICAM-1 (75 %) and P-selectin (72 %). mAbs to ICAM-1 or P-selectin, when used alone, could only slightly reduce the adhesion of monocyte to HUVEC. When both monoclonal antibodies were used in combination, the adhesion was markedly inhibited from 16.7 % to 11.3 % (P < 0.01), but the effect was still weaker than that of PBC (average 9.3 %). CONCLUSION: PBC exerts its inhibitory effect on the adhesion of monocyte to HUVEC by inhibiting the expression of ICAM-1 and P-selectin.
