Taban C H, Hondermarck H, Bradshaw R A, Biolly B
Centre de Biologie Cellulaire, Université de Lille, F-59655 Villeneuved'Ascq Cedex, France.
Experientia. 1996 Sep 15;52(9):865-70. doi: 10.1007/BF01938871.
The dipeptide Leu-Ala, which inhibits ubiquitin-mediated protein degradation, has been shown to act in vitro as an inhibitor of neurite outgrowth of PC12 cells (Hondermarck et al. [1992] Biochem. Biophys. Res. Commun. 189:280). Using agarose beads as vehicles, we tested, in vivo, the effect of this dipeptide (and the inactive inverse, Ala-Leu, as a control) on limb regeneration in the newt (Triturus cristatus), a nerve-dependent developmental process. Leu-Ala inhibited the growth of mid-bud blastemas without altering blastema differentiation, while Ala-Leu had no effect. Cytological observations of dipeptide-treated blastemas using Bodian staining or neurofilament antibodies showed that all the blastema tissues were unmodified except with regard to innervation. Leu-Ala-treated blastemas were devoid of nerve fibers in the epidermal cap, while the mesenchyme distal to the dipeptide impregnated bead exhibited fewer nerve fibers than did Ala-Leu-treated blastemas, which were similar to the control nontreated blastemas. Thus, Leu-Ala, in reducing blastema innervation, inhibits its growth in the same manner as surgical denervation.
二肽亮氨酸 - 丙氨酸可抑制泛素介导的蛋白质降解，已证明其在体外可作为PC12细胞神经突生长的抑制剂（Hondermarck等人，[1992]《生物化学与生物物理研究通讯》189:280）。我们以琼脂糖珠作为载体，在体内测试了这种二肽（以及无活性的反向肽丙氨酸 - 亮氨酸作为对照）对蝾螈（Triturus cristatus）肢体再生的影响，这是一个依赖神经的发育过程。亮氨酸 - 丙氨酸抑制中芽胚基的生长，但不改变胚基分化，而丙氨酸 - 亮氨酸则没有影响。使用博迪安染色或神经丝抗体对经二肽处理的胚基进行细胞学观察表明，除了神经支配方面外，所有胚基组织均未改变。经亮氨酸 - 丙氨酸处理的胚基在表皮帽中没有神经纤维，而在二肽浸渍珠远端的间充质中，神经纤维比经丙氨酸 - 亮氨酸处理的胚基少，后者与未处理的对照胚基相似。因此，亮氨酸 - 丙氨酸通过减少胚基的神经支配，以与手术去神经相同的方式抑制其生长。
