Tomás-Zapico Cristina, Coto-Montes Ana
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
J Pineal Res. 2005 Sep;39(2):99-104. doi: 10.1111/j.1600-079X.2005.00248.x.
Melatonin, the main secretory product of the pineal gland, is known to collaborate against oxidative stress within cells, but its mechanism of action in terms of stimulating antioxidant enzymes remains unclear. Herein, we propose that melatonin modulates antioxidant enzyme activities via its interaction with calmodulin, which in turn inhibits downstream processes that lead to the inactivation of nuclear RORalpha melatonin receptor. Eventually, this nuclear transcription factor downregulates NF-kappaB-induced antioxidant enzyme expression. Therefore, the increment in antioxidant enzyme activities induced by melatonin involves the inhibition of the RORalpha pathway. Thus, in addition to its direct free radical scavenging activities, melatonin has important actions in oxidative defense by stimulating enzymes which metabolize free radicals and radical products to innocuous metabolites.
褪黑素是松果体的主要分泌产物，已知其可协同对抗细胞内的氧化应激，但其刺激抗氧化酶的作用机制仍不清楚。在此，我们提出褪黑素通过与钙调蛋白相互作用来调节抗氧化酶活性，进而抑制导致核RORα褪黑素受体失活的下游过程。最终，这种核转录因子下调NF-κB诱导的抗氧化酶表达。因此，褪黑素诱导的抗氧化酶活性增加涉及对RORα途径的抑制。因此，除了其直接的自由基清除活性外，褪黑素通过刺激将自由基和自由基产物代谢为无害代谢物的酶，在氧化防御中具有重要作用。
