Fontaine-Lenoir Virginie, Chambraud Béatrice, Fellous Arlette, David Sébastien, Duchossoy Yann, Baulieu Etienne-Emile, Robel Paul
MAPREG Company, Centre Hospitalier Universitaire de Bicêtre, Bâtiment Paul Langevin, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France.
Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4711-6. doi: 10.1073/pnas.0600113103. Epub 2006 Mar 14.
The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3beta-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) and stimulate the polymerization of microtubules. PREG, MePREG, and progesterone (PROG; the physiological immediate metabolite of PREG) significantly enhance neurite outgrowth of nerve growth factor-pretreated PC12 cells. However, PROG, although it binds to MAP2, does not increase the immunostaining of MAP2, contrary to PREG and MePREG. Nocodazole, a microtubule-disrupting agent, induces a major retraction of neurites in control cultures, but pretreatment with PREG/MePREG is protective. Decreasing MAP2 expression by RNA interference does not modify PROG action, but it prevents the stimulatory effects of PREG and MePREG on neurite extension, showing that MAP2 is their specific receptor.
神经甾体孕烯醇酮(PREG)及其化学合成类似物3β-甲氧基孕烯醇酮(MePREG)与微管相关蛋白2(MAP2)结合并刺激微管聚合。PREG、MePREG和孕酮(PROG;PREG的生理直接代谢产物)显著增强神经生长因子预处理的PC12细胞的神经突生长。然而,PROG虽然与MAP2结合,但与PREG和MePREG相反,它不会增加MAP2的免疫染色。诺考达唑是一种破坏微管的药物,在对照培养物中可诱导神经突大量回缩,但用PREG/MePREG预处理具有保护作用。通过RNA干扰降低MAP2表达不会改变PROG的作用,但会阻止PREG和MePREG对神经突延伸的刺激作用,表明MAP2是它们的特异性受体。