MYOBLAST FUSION IS REGULATED BY A PROSTANOID OF THE ONE SERIES INDEPENDENTLY OF A RISE IN CYCLIC-AMP
MYOBLAST FUSION IS REGULATED BY A PROSTANOID OF THE ONE SERIES INDEPENDENTLY OF A RISE IN CYCLIC-AMP
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DOI：
10.1083/jcb.103.3.857
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发表时间：
1986-09-01
影响因子：
7.8
通讯作者：
ZALIN, RJ
中科院分区：
文献类型：
--
作者：
ENTWISTLE, A;CURTIS, DH;ZALIN, RJ
研究了前列腺素类在鸡成肌细胞分化调节中的作用。在3倍。10-6消炎痛和氯喹特异性抑制细胞融合。它们不影响细胞增殖、排列或两种肌肉特异性蛋白质的表达，即乙酰胆碱受体和肌酸磷酸激酶的肌肉特异性形式。结果表明，吲哚美辛作为环加氧酶步骤前列腺素合成的抑制剂的活性导致细胞融合的阻断，而氯喹可能作用于磷脂酶A的早期步骤。前列腺素E1（PGE 1），而不是前列腺素E2（PGE 2），迅速逆转由消炎痛或氯喹施加的融合抑制。成肌细胞对PGE 1的剂量反应是钟形曲线，在λ时融合100%逆转。10-9 M.二十碳三烯酸盐和亚油酸盐以类似的动力学逆转融合的抑制，而花生四烯酸盐完全无效。PGE 1和二十碳三烯酸盐而不是PGE 2和花生四烯酸盐将融合恢复到对照水平的能力意味着融合是由一系列的前列腺素类特异性调节的。亚油酸对融合阻滞的逆转进一步表明，这种脂肪酸为成肌细胞质膜中的二十碳三烯酸提供了必要的来源。在10-8 M及以上，PGE 1和PGE 2刺激腺苷酸环化酶和抑制控制融合，如10-5 M异丙肾上腺素。β-肾上腺素能阻滞剂普萘洛尔消除了异丙肾上腺素对成肌细胞融合的抑制及其对腺苷酸环化酶的激活。10-8-10-6 M前列腺素和10-5 M异丙肾上腺素对细胞融合产生的类似抑制作用表明，在这两种情况下，抑制作用均由环AMP介导。它的结论是一个系列的前列腺素调节融合的一个循环AMP独立的机制。
The role of prostanoids in the regulation of chick myoblast differentiation has been investigated. At 3 .times. 10-6 M, indomethacin and chloroquine specifically inhibit cell fusion. They do not affect cell proliferation, alignment, or the expression of two muscle-specific proteins, namely, the acetylcholine receptor and the muscle-specific form of creatine phosphokinase. The results demonstrate that it is indomethacin''s activity as an inhibitor of prostaglandin synthesis at the cyclooxygenase step that causes the block of cell fusion, whereas chloroquine probably acts at the earlier step of phospholipase A. Prostaglandin E1 (PGE1), but not prostaglandin E2 (PGE2), rapidly reverses the inhibition of fusion imposed by indomethacin or chloroquine. The dose response of the myoblasts to PGE1 is a bell-shaped curve with a 100% reversal of fusion at .apprx. 10-9 M. Eicosatrienoate and linoleate reverse the inhibition of fusion with similar kinetics, whereas arachidonate is completely ineffective. The ability of PGE1 and eicosatrienoate but not PGE2 and arachidonate to restore fusion to control levels implies that fusion is specifically regulated by a prostanoid of the one series. The reversal of the fusion-block by linoleate further suggests that this fatty acid provides the necessary source of eicosatrienoate in the myoblast plasma membrane. At 10-8 M and above, PGE1 and PGE2 stimulate adenylate cyclase and depress control fusion as does 10-5 M isoproterenol. The .beta.-adrenergic blocker propranolol abolishes both isoproterenol''s inhibition of myoblast fusion and its activation of adenylate cyclase. The similar depressions imposed on cell fusion by 10-8-10-6 M prostanoid and 10-5 M isoproterenol suggest that in both cases the depressive effects are mediated by cyclic AMP. It is concluded that a prostanoid of the one series regulates fusion by a cyclic AMP-independent mechanism.