Vassaux G, Gaillard D, Ailhaud G, Négrel R
Centre de Biochimie du Centre National de la Recherche Scientifique (UMR 134), Faculté des Sciences, Université de Nice-Sophia Antipolis, Parc Valrose, France.
J Biol Chem. 1992 Jun 5;267(16):11092-7.
The mitogenic-adipogenic activity of carbaprostacyclin (cPGI2), a stable analogue of prostacyclin (PGI2), has been proposed to be related to its ability to elicit cAMP production and to activate the protein kinase A cascade (Négrel, R., Gaillard, D., and Ailhaud, G. (1989) Biochem. J. 257, 399-405). In the present study, cPGI2 has been compared with other activators of the cAMP pathway, namely isoproterenol, forskolin and 8-bromo-cAMP, with respect to adipose cell differentiation. Carbaprostacyclin behaved as a much more potent and efficient effector of mouse Ob1771 preadipocyte differentiation than the latter agents. Moreover, cPGI2 also exerted a specific amplifying mitogenic-adipogenic role, as compared with isoproterenol in rat as well as human adipose precursor cells in primary culture, suggesting that the prostanoid was able to generate an additional second messenger. The fact that ionomycin was able to potentiate and amplify the differentiation induced by 8-bromo-cAMP led us to give evidence, using preadipocytes preloaded with the fluorescent calcium chelator Indo-1, that cPGI2, besides its ability to activate adenyl cyclase, was also able to induce a transient increase in intracellular free calcium. This phenomenon was independent of cAMP production or inositol phospholipid breakdown and appeared to be mediated after binding to a single class of PGI2 receptor. The potential to generate simultaneously two synergistic intracellular signals allows us to ascribe to PGI2 a key and specific role in the differentiation of adipose precursor cells in vitro that would likely lead in vivo to the recruitment of "dormant" preadipocytes to become adipocytes.
卡前列环素（cPGI2）是前列环素（PGI2）的一种稳定类似物，其促有丝分裂 - 脂肪生成活性被认为与其引发环磷酸腺苷（cAMP）产生及激活蛋白激酶A级联反应的能力有关（内格雷尔，R.，加亚尔，D.，以及艾洛德，G.（1989年）《生物化学杂志》257卷，399 - 405页）。在本研究中，就脂肪细胞分化而言，已将cPGI2与cAMP途径的其他激活剂，即异丙肾上腺素、福斯高林和8 - 溴 - cAMP进行了比较。与后几种试剂相比，卡前列环素对小鼠Ob1771前脂肪细胞分化的作用更强且更有效。此外，与异丙肾上腺素相比，cPGI2在原代培养的大鼠以及人脂肪前体细胞中也发挥了特定的促有丝分裂 - 脂肪生成放大作用，这表明该前列腺素能够产生额外的第二信使。离子霉素能够增强并放大8 - 溴 - cAMP诱导的分化这一事实，促使我们利用预先加载荧光钙螯合剂Indo - 1的前脂肪细胞来证明，cPGI2除了具有激活腺苷酸环化酶的能力外，还能够诱导细胞内游离钙的短暂增加。这种现象独立于cAMP的产生或肌醇磷脂的分解，并且似乎是在与单一类别的PGI2受体结合后介导的。同时产生两种协同细胞内信号的潜力使我们能够将PGI2在体外脂肪前体细胞分化中所起的关键且特定作用归因于它，这在体内可能会导致“休眠”的前脂肪细胞被募集成为脂肪细胞。
