Espino Javier, Bejarano Ignacio, Paredes Sergio D, Barriga Carmen, Reiter Russel J, Pariente José A, Rodríguez Ana B
Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain.
Age (Dordr). 2011 Dec;33(4):497-507. doi: 10.1007/s11357-010-9194-0. Epub 2010 Nov 18.
The mechanisms regulating neutrophil apoptosis are basically unaffected by the aging process. However, a significant impairment of cell survival occurs in elderly individuals following neutrophil challenge with pro-inflammatory stimuli, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). The goal of the present study was to prove the effects of melatonin supplementation on apoptosis induced by calcium signaling in human leukocytes from elderly volunteers. Treatments with the specific inhibitor of cytosolic calcium re-uptake, thapsigargin, and/or the calcium mobilizing agonist, N-formyl-methionyl-leucyl-phenylalanine (fMLP), induced mitochondrial membrane depolarization, caspase activation, phosphatidylserine (PS) externalization, and DNA fragmentation in leukocytes from both young and elderly volunteers, although such effects were much more evident in aged leukocytes. Importantly, melatonin treatment substantially preserved mitochondrial membrane potential, reversed caspase activation, reduced PS exposure and forestalled DNA fragmentation in leukocytes from both age groups. In conclusion, melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in aged leukocytes and may counteract, at the cellular level, age-related degenerative phenomena linked to oxidative stress.
调节中性粒细胞凋亡的机制基本上不受衰老过程的影响。然而，在老年个体中，用促炎刺激物（如粒细胞-巨噬细胞集落刺激因子（GM-CSF））刺激中性粒细胞后，细胞存活会出现显著受损。本研究的目的是证明补充褪黑素对老年志愿者人白细胞中钙信号诱导的凋亡的影响。用胞质钙再摄取的特异性抑制剂毒胡萝卜素和/或钙动员激动剂N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）处理，可诱导年轻和老年志愿者白细胞中的线粒体膜去极化、半胱天冬酶激活、磷脂酰丝氨酸（PS）外化和DNA片段化，尽管这些效应在老年白细胞中更为明显。重要的是，褪黑素处理在很大程度上保留了两个年龄组白细胞的线粒体膜电位，逆转了半胱天冬酶激活，减少了PS暴露并阻止了DNA片段化。总之，褪黑素能够延迟老年白细胞内质网应激诱导的凋亡，并可能在细胞水平上抵消与氧化应激相关的年龄相关性退行性现象。
