Age-related alterations in Ca2+ signals and mitochondrial membrane potential in exocrine cells are prevented by melatonin
Age-related alterations in Ca2+ signals and mitochondrial membrane potential in exocrine cells are prevented by melatonin
复制标题
DOI：
10.1111/j.1600-079x.2008.00576.x
复制
发表时间：
2008-09-01
影响因子：
10.3
通讯作者：
Camello, Pedro J.
中科院分区：
文献类型：
--
作者：
Camello-Almaraz, Cristina;Gomez-Pinilla, Pedro J.;Camello, Pedro J.
关于不可兴奋细胞中年龄诱导的Ca2+信号改变的信息是有限的。此外，很少有证据表明褪黑素能够缓解衰老对Ca2+信号和线粒体电位的影响，这是一个涉及Ca2+信号和衰老的参数。我们研究了褪黑激素防止衰老对外分泌细胞内Ca2+稳态和线粒体电位的影响的能力。采用胶原酶分散法分别获得成年（3月龄）和老年（22-24月龄）小鼠胰腺腺泡细胞。测定Ca2+信号、线粒体原位电位和体外淀粉酶分泌。随着分泌剂乙酰胆碱和胆囊收缩素（CCK）水平的升高，老年胰腺腺泡的分泌受到损害。这种减少伴随着对激动剂最大浓度的峰响应幅度的抑制，以及餐后CCK水平诱导的Ca2+振荡模式的减少。在衰老的细胞中，钙池的大小（通过低水平的离子霉素来评估）和由thapsigarin耗尽储存引起的容性钙进入都减少了。这些Ca2+稳态的变化与细胞内线粒体的去极化有关。口服褪黑素3个月后，老龄小鼠的分泌反应、Ca2+反应的幅度和频率、细胞内钙池的大小、容性钙进入和线粒体电位得以恢复。综上所述，褪黑素可以恢复衰老外分泌细胞的分泌功能、Ca2+信号和线粒体电位。
Information regarding age-induced Ca2+ signal alterations in nonexcitable cells is limited. In addition, little evidence exists on the ability of melatonin to palliate the effects of aging on Ca2+ signals and mitochondrial potential, a parameter involved in both Ca2+ signaling and aging. We studied the ability of melatonin to prevent the effects of aging on intracellular Ca2+ homeostasis and mitochondrial potential in exocrine cells. Pancreatic acinar cells were obtained from adult (3 months old) and aged (22-24 months old) mice by collagenase dispersion. Ca2+ signals, in situ mitochondrial potential and in vitro amylase secretion were determined. Secretion in response to increasing levels of the secretagogues, acetylcholine and cholecystokinin (CCK), were impaired in aged pancreatic acini. This decrease was accompanied by an inhibition in the amplitude of the peak response to maximal concentrations of the agonists, and by a decrease in the pattern of Ca2+ oscillations induced by postprandial levels of CCK. Both the size of the calcium pools, assessed by low levels of ionomycin, and capacitative calcium entry, induced by depletion of the stores with thapsigargin, were diminished in aged cells. These changes in Ca2+ homeostasis were associated with depolarization of intracellular mitochondria. Oral administration of melatonin for 3 months to aged mice restored the secretory response, the amplitude and frequency of Ca2+ responses, the size of intracellular calcium pools, the capacitative calcium entry, and the mitochondrial potential. In conclusion, melatonin restores secretory function, Ca2+ signals and mitochondrial potential of aged exocrine cells.