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    题名: Humic acid induces apoptosis in human endothelial cells
    作者: Hseu, YC;Huang, HW;Wang, SY;Chen, HY;Lu, FJ;Gau, RJ;Yang, HL
    贡献者: 健康照護學院營養系;China Med Univ, Inst Nutr, Taichung 40421, Taiwan;Fooyin Inst Technol, Dept Med Technol, Kaohsiung, Taiwan;Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan;Natl Taiwan Univ, Coll Med, Dept Biochem, Taipei 10018, Taiwan
    日期: 2002
    上传时间: 2010-09-24 14:33:55 (UTC+8)
    出版者: ACADEMIC PRESS INC ELSEVIER SCIENCE
    摘要: Because the metabolites of arachidonic acid participate in many physiopathological responses, including inflammation and platelet aggregation, cyclooxygenase inhibitors are important in the treatment of associated diseases. A biologically active compound, 5-ethyl-4-methoxy-2-phenylquinoline (KTC-5), selectively and concentration dependently inhibited aggregation of platelets from man and ATP release caused by arachidonic acid (200 mum) and collagen (10 mug mL(-1)) without affecting the aggregation caused by thrombin (0.1 U mL(-1)) and U46619 (2 mum). The IC50 value (drug concentration inhibiting maximum response by 50%) of KTC-5 for aggregation induced by arachidonic acid and collagen was 0.11 +/- 0.04 mum and 0.20 +/- 0.03 mum, respectively. This inhibitory effect of KTC-5 was reversible and time dependent. KTC-5 specifically inhibited intracellular calcium mobilization initiated by arachidonic acid or collagen without affecting that caused by thrombin or U46619 in human platelets. Furthermore, KTC-5 inhibited thromboxane B-2 and prostaglandin D-2 formation provoked by arachidonic acid. The IC50 value of KTC-5 for arachidonic-acid-induced thromboxane B-2 formation was 0.07 +/- 0.02 mum. Based on these observations, the data indicated that KTC-5 potently inhibited human platelet aggregation and ATP release mainly via the inhibition of the cyclooxygenase-1 activity. Moreover, KTC-5 inhibited lipopolysaccharide-induced prostaglandin E-2 formation in RAW264.7 cells in the presence of external arachidonic acid with an IC50 value of 0.17 +/- 0.06 mum. Immunoblot analysis showed that KTC-5 did not affect the cyclooxygenase-2 expression in the presence of lipopolysaccharide on RAW264.7 cells. This result indicated that KTC-5 affects the activity of cyclooxygenase-2. According to these data, we concluded that KTC-5 is a cyclooxygenase inhibitor for both subtypes.
    關聯: TOXICOLOGY AND APPLIED PHARMACOLOGY 182(1):34-43
    显示于类别:[營養學系暨碩士班 ] 期刊論文

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