Radogna Flavia, Paternoster Laura, Albertini Maria Cristina, Cerella Claudia, Accorsi Augusto, Bucchini Anahi, Spadoni Gilberto, Diamantini Giuseppe, Tarzia Giorgio, De Nicola Milena, D'Alessio Maria, Ghibelli Lina
Dipartimento di Biologia, Università di Roma Tor Vergata, Rome, Italy.
J Pineal Res. 2007 Sep;43(2):154-62. doi: 10.1111/j.1600-079X.2007.00455.x.
Among the non-neurological functions of melatonin, much attention is being directed to the ability of melatonin to modulate the immune system, whose cells possess melatonin-specific receptors and biosynthetic enzymes. Melatonin controls cell behaviour by eliciting specific signal transduction actions after its interaction with plasma membrane receptors (MT(1), MT(2)); additionally, melatonin potently neutralizes free radicals. Melatonin regulates immune cell loss by antagonizing apoptosis. A major unsolved question is whether this is due to receptor involvement, or to radical scavenging considering that apoptosis is often dependent on oxidative alterations. Here, we provide evidence that on U937 monocytic cells, apoptosis is antagonized by melatonin by receptor interaction rather than by radical scavenging. First, melatonin and a set of synthetic analogues prevented apoptosis in a manner that is proportional to their affinity for plasma membrane receptors but not to their antioxidant ability. Secondly, melatonin's antiapoptotic effect required key signal transduction events including G protein, phospholipase C and Ca(2+) influx and, more important, it is sensitive to the specific melatonin receptor antagonist luzindole.
在褪黑素的非神经功能中，其调节免疫系统的能力备受关注，免疫细胞拥有褪黑素特异性受体和生物合成酶。褪黑素与质膜受体（MT(1)、MT(2)）相互作用后，通过引发特定的信号转导作用来控制细胞行为；此外，褪黑素能有效中和自由基。褪黑素通过拮抗细胞凋亡来调节免疫细胞的损失。一个主要未解决的问题是，这是由于受体参与，还是考虑到细胞凋亡通常依赖于氧化改变而通过自由基清除作用导致的。在此，我们提供证据表明，在U937单核细胞上，褪黑素通过受体相互作用而非自由基清除作用来拮抗细胞凋亡。首先，褪黑素和一组合成类似物以与其对质膜受体的亲和力成正比而非与其抗氧化能力成正比的方式阻止细胞凋亡。其次，褪黑素的抗凋亡作用需要关键的信号转导事件，包括G蛋白、磷脂酶C和Ca(2+)内流，更重要的是，它对特异性褪黑素受体拮抗剂鲁辛朵敏感。
