Caspase 3 activation in human spermatozoa in response to hydrogen peroxide and progesterone
Caspase 3 activation in human spermatozoa in response to hydrogen peroxide and progesterone
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DOI：
10.1016/j.fertnstert.2007.08.069
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发表时间：
2008-10-01
影响因子：
6.7
通讯作者：
Pariente, Jose A.
中科院分区：
文献类型：
--
作者：
Bejarano, Ignacio;Lozano, Graciela M.;Pariente, Jose A.
目的：研究钙信号在活性氧H2 O2和生理激动剂P诱导的人精子凋亡中的作用。设计：实验室研究。单位：西班牙一家医院的人类辅助生殖中心。患者：45名健康志愿者。干预措施：用浓度递增的过氧化氢（H2 O2; 10 μ M、100 μ M和1 mM）或20 μ M的P处理精子5-120分钟。主要结局指标：用荧光法检测了人精子中caspase-3和caspase-9的激活以及磷脂酰丝氨酸的外化。结果：过氧化氢和P诱导caspase-3和-9活化。此外，H_2O_2和P的作用具有时间依赖性。二甲基-1，2-双（氨基苯氧基）乙烷-N，N，N '，N '-四乙酸负载能够抑制H2 O2和P诱导的caspase-3激活和磷脂酰丝氨酸外化。Ru 360预处理精子，以阻止钙摄入线粒体，也能够减少caspase-3的激活和磷脂酰丝氨酸暴露，由H2 O2或P刺激。结论：这些发现表明，H2 O2和P诱导的线粒体凋亡依赖于钙信号。
Objective: To determine the role of calcium signaling on apoptosis evoked by the reactive oxygen species H2O2 and by the physiological agonist P in human ejaculated spermatozoa. Design: Laboratory study. Setting: Center for assisted human reproduction in a hospital in Spain. Patient(s): Forty-five healthy volunteers. Intervention(s): Spermatozoa were treated with increasing concentrations of hydrogen peroxide (H2O2; 10 mu M, 100 mu M, and 1 mM) or with 20 mu M of P for 5-120 minutes. Main Outcome Measure(s): Activation of caspase-3 and -9 as well as phosphatidylserine externalization were examined in human ejaculated spermatozoa by fluorescence methods. Result(s): Hydrogen peroxide and P induced activation of caspase-3 and -9. In addition, the effect of H2O2 and P was time dependent. Dimethyl-1,2-bis (aminophenoxy) ethane-N,N,N ',N '-tetraacetic acid loading was able to inhibit H2O2- and P-induced caspase-3 activation and phosphatidylserine externalization. Pretreatment of spermatozoa with Ru360, to block the calcium uptake into mitochondria, also was able to decrease the activation of caspase-3 and phosphatidylserine exposure that was stimulated by either H2O2 or P. Conclusion(s): These findings suggest that H2O2- and P-induced mitochondrial apoptosis is dependent on calcium signaling.