Progesterone-stimulated intracellular calcium increase in human spermatozoa is protein kinase C-independent.
Progesterone-stimulated intracellular calcium increase in human spermatozoa is protein kinase C-independent.
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黄体酮刺激人类精子细胞内钙的增加不依赖于蛋白激酶 C。
DOI：
--
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发表时间：
1998
影响因子：
4
通讯作者：
Elisabetta Baldi
中科院分区：
文献类型：
--
作者：
L. Bonaccorsi;Csilla Krausz;Paola Pecchioli;Gianni Forti;Elisabetta Baldi
间接研究表明，蛋白激酶C（PKC）在精子运动和顶体反应中起作用。精子顶体反应的生理诱导剂包括孕酮，其可以增加人精子中的细胞内钙（[Ca 2 +]i）、蛋白质的酪氨酸磷酸化和氯流出。PKC可能参与了孕酮刺激的顶体反应，尽管关于PKC抑制对孕酮刺激的[Ca 2 +]i增加的影响已经获得了有争议的结果。在本研究中，我们研究了孕酮对PKC活性的直接影响，以及一组PKC抑制剂对孕酮刺激的[Ca2+]i增加和蛋白质酪氨酸磷酸化的影响。我们发现，孕酮刺激精子PKC活性和PKC抑制与星形孢菌素和bisindolylmaleimide部分逆转孕酮对顶体反应的影响，表明参与的酶的类固醇的效果。接下来，我们评估了三种不同的PKC抑制剂（桑戈霉素、星形孢菌素和双吲哚马来酰亚胺）对孕酮刺激的[Ca 2 +]i增加的影响。无论是短期（15分钟）或长期（90分钟）预孵育的任何三种化合物有一个显着的效果孕酮对精子[Ca 2 +]i的刺激作用。也不是孕激素的反应受到短期（确定激活的PKC）或长期（确定下调的PKC）与肿瘤促进剂佛波醇肉豆蔻酸酯（PMA），一个已知的非生理刺激剂的PKC孵育。这些结果表明，孕酮刺激的钙内流是独立的PKC激活。此外，我们发现，与PKC抑制剂预孵育本身对精子蛋白的酪氨酸磷酸化有刺激作用。与适当的对照相比，孕酮对酪氨酸磷酸化的影响被抑制剂桑戈霉素、星形孢菌素和双吲哚马来酰亚胺轻微（但不显著）降低，但被钙磷素C显著抑制。这些结果不允许PKC参与孕酮刺激的精子蛋白酪氨酸磷酸化的最终结论。然而，PMA对酪氨酸磷酸化作用的缺乏表明PKC刺激不足以诱导这种作用。总之，我们的研究结果表明，PKC在甾体酮诱导的顶体反应中起作用，甾体酮刺激的PKC激活是甾体激素刺激钙内流的下游。
Indirect studies suggested that protein kinase C (PKC) has a role in sperm motility and the acrosome reaction. Physiological inducers of the sperm acrosome reaction include progesterone, which can increase intracellular calcium ([Ca2+]i), tyrosine phosphorylation of proteins and chloride efflux in human spermatozoa. PKC may be involved in progesterone-stimulated acrosome reaction, although controversial results have been obtained concerning the effect of PKC inhibition on progesterone-stimulated [Ca2+]i increase. In the present study, we investigated the direct effect of progesterone on the activity of PKC, as well as the effect of a panel of PKC inhibitors on progesterone-stimulated [Ca2+]i increase and tyrosine phosphorylation of proteins. We found that progesterone stimulates sperm PKC activity and that PKC inhibition with staurosporine and bisindolylmaleimide partially reversed the effect of progesterone on acrosome reaction, indicating an involvement of the enzyme in the effect of the steroid. We next evaluated the effect of three different PKC inhibitors (sangivamycin, staurosporine and bisindolylmaleimide) on progesterone-stimulated [Ca2+]i increase. Neither short-term (15 min) nor long-term (90 min) preincubation with any of the three compounds had a substantial effect on the stimulatory effect of progesterone on sperm [Ca2+]i. Nor was responsiveness to progesterone affected by either short-term (determining activation of PKC) or long-term (determining down-regulation of PKC) incubation with the tumour promoter phorbol myristate acetate (PMA), a known non-physiological stimulator of PKC. These results indicate that progesterone-stimulated calcium influx is independent of PKC activation. In addition, we found that preincubation with PKC inhibitors had a stimulatory effect per se on tyrosine phosphorylation of sperm proteins. When compared with the appropriate control, the effect of progesterone on tyrosine phosphorylation was slightly (but not significantly) reduced by the inhibitors, sangivamycin, staurosporine and bisindolylmaleimide, but was significantly inhibited by calphostin C. These results do not permit a final conclusion on the involvement of PKC in progesterone-stimulated tyrosine phosphorylation of sperm proteins. However, the lack of effect of PMA on tyrosine phosphorylation indicates that PKC stimulation is not sufficient to induce this effect. In conclusion, our results indicate that PKC plays a role in progesterone-induced acrosome reaction and that progesterone-stimulated PKC activation is downstream to stimulation of calcium influx by the steroid.
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受精时人类精子的酪氨酸激酶与透明带的相互作用。
DOI：
10.1126/science.7541556
发表时间：
1995
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burks,DJ;Carballada,R;Moore,HD;Saling,PM
通讯作者：
Saling,PM
影响因子：
11.2
作者：
T. Sako;A. Tauber;A. Jeng;S. Yuspa;P. Blumberg
通讯作者：
T. Sako;A. Tauber;A. Jeng;S. Yuspa;P. Blumberg
影响因子：
2.7
作者：
Carrera, A;Moos, J;Moss, SB
通讯作者：
Moss, SB
长期佛波酯治疗可下调蛋白激酶 C 并使磷酸肌醇信号通路对激素和生长因子刺激敏感。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hepler,JR;Earp,HS;Harden,TK
通讯作者：
Harden,TK
激活的人中性粒细胞中的酪氨酸磷酸化。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rollet,E;Caon,AC;Roberge,CJ;Liao,NW;Malawista,SE;McColl,SR;Naccache,PH
通讯作者：
Naccache,PH