Department of Physiology, University of Extremadura, Badajoz, Spain.
J Membr Biol. 2010 Feb;233(1-3):105-18. doi: 10.1007/s00232-010-9230-0. Epub 2010 Feb 4.
We have evaluated the effect of melatonin on apoptosis evoked by increases in Ca(2+) in human leukocytes. Our results show that treatment of neutrophils with the calcium mobilizing agonist FMLP or the specific inhibitor of calcium reuptake thapsigargin induced a transient increase in Ca(2+). Our results also show that FMLP and thapsigargin increased caspase-9 and -3 activities and the active forms of both caspases. The effect of FMLP and thapsigargin on caspase activation was time-dependent. Similar results were obtained when lymphocytes were stimulated with thapsigargin. This stimulatory effect was accompanied by induction of mPTP, activation of the proapoptotic protein Bax and release of cytochrome c. However, when leukocytes were pretreated with melatonin, all of the apoptotic features indicated above were significantly reversed. Our results suggest that melatonin reduces caspase-9 and -3 activities induced by increases in Ca(2+) in human leukocytes, which are produced through the inhibition of both mPTP and Bax activation.
我们评估了褪黑素对人白细胞中钙离子浓度增加引起的细胞凋亡的影响。结果显示，钙离子载体佛波醇酯（FMLP）或钙离子重摄取抑制剂 thapsigargin 处理中性粒细胞可引起Ca(2+)的短暂增加。结果还显示，FMLP 和 thapsigargin 增加了 caspase-9 和 -3 的活性以及这两种半胱天冬酶的活性形式。FMLP 和 thapsigargin 对 caspase 激活的影响具有时间依赖性。当淋巴细胞用 thapsigargin 刺激时，也得到了类似的结果。这种刺激作用伴随着 mPTP 的诱导、促凋亡蛋白 Bax 的激活和细胞色素 c 的释放。然而，当白细胞用褪黑素预处理时，上述所有凋亡特征都明显逆转。结果表明，褪黑素通过抑制 mPTP 和 Bax 的激活，降低了人白细胞中Ca(2+)增加诱导的 caspase-9 和 -3 活性。
