Altmann Anja, Fischer Lutz, Schubert-Zsilavecz Manfred, Steinhilber Dieter, Werz Oliver
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):185-90. doi: 10.1006/bbrc.2001.6153.
Here we show that extracts of Boswellia serrata gum resins and its constituents, the boswellic acids (BAs), activate the mitogen-activated protein kinases (MAPK) p42(MAPK) and p38 in isolated human polymorphonuclear leukocytes (PMNL). MAPK activation was rapid and transient with maximal activation after 1-2.5 min of exposure and occurred in a dose-dependent manner. The keto-BAs (11-keto-beta-BA and 3-O-acetyl-11-beta-keto-BA) gave substantial kinase activation at 30 microM, whereas other BAs lacking the 11-keto group were less effective. Moreover, 11-keto-BAs induced rapid and prominent mobilization of free Ca(2+) in PMNL. Inhibitor studies revealed that phosphatidylinositol 3-kinase (PI 3-K) is involved in BA-induced MAPK activation, whereas a minor role was apparent for protein kinase C. MAPK activation by 3-O-acetyl-11-beta-keto-BA was partially inhibited when Ca(2+) was removed by chelation. Our results suggest that 11-keto-BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Ca(2+).
在此我们表明，乳香树胶树脂提取物及其成分乳香酸（BAs）可激活分离的人多形核白细胞（PMNL）中的丝裂原活化蛋白激酶（MAPK）p42（MAPK）和p38。MAPK的激活迅速且短暂，暴露1 - 2.5分钟后激活达到最大值，并且呈剂量依赖性。酮基乳香酸（11 - 酮基 - β - 乳香酸和3 - O - 乙酰基 - 11 - β - 酮基 - 乳香酸）在30微摩尔浓度时可使激酶大量激活，而其他不含11 - 酮基的乳香酸效果较差。此外，11 - 酮基乳香酸可诱导PMNL中游离Ca(2+)的快速且显著的动员。抑制剂研究表明，磷脂酰肌醇3 - 激酶（PI 3 - K）参与了乳香酸诱导的MAPK激活，而蛋白激酶C的作用较小。当通过螯合去除Ca(2+)时，3 - O - 乙酰基 - 11 - β - 酮基 - 乳香酸诱导的MAPK激活受到部分抑制。我们的结果表明，11 - 酮基乳香酸可能通过刺激MAPK和动员细胞内Ca(2+)而作为PMNL的有效激活剂发挥作用。
