Benítez-King G, Huerto-Delgadillo L, Antón-Tay F
Departmento de Neurofarmacología, Instituto Mexicano de Psiquiatría Mexico.
J Pineal Res. 1990;9(3):209-20. doi: 10.1111/j.1600-079x.1990.tb00709.x.
Despite the fact that many physiological and pharmacological actions of melatonin (MEL) have been described, its mechanism of action at the subcellular level remains unclear. It has been suggested that MEL has effects on cellular processes that involve microfilaments and microtubules. In the present study MEL effects on the cytoskeleton were evaluated in MDCK and N1E-115 cells in which the microfilaments have been shown to participate in cell morphology and dome formation (MDCK) and the microtubules in neurite outgrowths. After one day of culture with 10(-11)-10(-7) M MEL MDCK cells showed an increase in the number of elongated cells. After four days with the hormone, an increase in the incidence of MDCK cells contacting neighboring cells through long cytoplasmic elongations was observed. Actin antibody stain showed the appearance of thicker fluorescent fibres beneath the cell membrane and over the nucleus in the MEL treated cells. An increase in dome formation in confluent cells was also observed. In N1E-115 cells MEL (10(-13)-10(-5) M) induced an increase in cell with neurite processes. Neurite outgrowth is clearly seen at 24 h after plating. MEL-treated cells grow in clusters with neurites forming intricate networks. Antitubulin antibody stain showed long fluorescent neurites in the N1E-115 MEL-treated cells. A decrease in N1E-115 neurite formation was observed with either serotonin or 6-hydroxymelatonin (6OH-MEL). However, the number of MDCK cells with cytoplasmic elongations was decreased only after 6OH-MEL. We conclude that MEL action at the cellular level involves a modification of the cytoskeletal organization.
尽管褪黑素（MEL）的许多生理和药理作用已被描述，但其在亚细胞水平的作用机制仍不清楚。有人提出，MEL对涉及微丝和微管的细胞过程有影响。在本研究中，在MDCK和N1E-115细胞中评估了MEL对细胞骨架的影响，其中已证明微丝参与细胞形态和穹顶形成（MDCK），微管参与神经突生长。用10^(-11)-10^(-7)M MEL培养一天后，MDCK细胞中伸长细胞的数量增加。用该激素处理四天后，观察到MDCK细胞通过长细胞质伸长与相邻细胞接触的发生率增加。肌动蛋白抗体染色显示，在MEL处理的细胞中，细胞膜下方和细胞核上方出现了更粗的荧光纤维。还观察到汇合细胞中穹顶形成增加。在N1E-115细胞中，MEL（10^(-13)-10^(-5)M）诱导有神经突的细胞增加。接种后24小时可清楚看到神经突生长。MEL处理的细胞成簇生长，神经突形成复杂的网络。抗微管蛋白抗体染色显示，在N1E-115 MEL处理的细胞中有长的荧光神经突。用血清素或6-羟基褪黑素（6OH-MEL）处理后，N1E-115神经突形成减少。然而，只有在6OH-MEL处理后，有细胞质伸长的MDCK细胞数量才减少。我们得出结论，MEL在细胞水平的作用涉及细胞骨架组织的改变。
