Contraceptive gossypol blocks cell-to-cell communication in human and rat cells
Contraceptive gossypol blocks cell-to-cell communication in human and rat cells
复制标题
DOI：
10.1016/0014-2999(96)00476-1
复制
发表时间：
1996-10-17
影响因子：
5
通讯作者：
Deleze, J
中科院分区：
文献类型：
--
作者：
Herve, JC;Pluciennik, F;Deleze, J
棉酚（一种天然存在于棉籽中的多环亲脂性试剂，被称为强效非类固醇抗生育剂和非特异性酶抑制剂）以剂量依赖性方式不可逆地损害了来自人或大鼠的各种培养细胞的同源对之间的细胞间通讯，这些细胞涉及（支持细胞或滋养层细胞）或不涉及（心室肌细胞）类固醇生成。在无血清测定中，在非细胞毒性条件下发生快速连接解偶联。在5 μ M（约两倍的峰值血浆浓度在人类患者中测得的慢性给药期间），间隙连接通信中断4至10分钟内，没有在细胞内Ca2+浓度的伴随上升。当棉酚处理时间延长时，后者显著增加（细胞毒性效应）。棉酚的短期解偶联作用被血清蛋白阻止，但持久的治疗（48小时）与中等浓度（3 μ M）引起交界解偶联，并阻碍了体外分化的人滋养层细胞。
Gossypol (a polycyclic lipophilic agent naturally present in cottonseed, known as a potent non-steroid antifertility agent and a non-specific enzyme inhibitor) irreversibly impaired the intercellular communication between homologous pairs of various cultured cells, from man or rat, involved (Sertoli or trophoblastic cells) or not involved (ventricular myocytes) in steroidogenesis, in a dose-dependent manner. In serum-free assays, a rapid junctional uncoupling occurred in non-cytotoxic conditions. At 5 mu M (approximately twice the peak plasma concentration measured in human patients during chronic administration), gap junctional communication was interrupted within 4 to 10 min, without concomitant rise in the intracellular Ca2+ concentration. The latter importantly increased when gossypol treatment was prolonged (cytotoxic effect). The short term uncoupling effect of gossypol was prevented by serum proteins, but long-lasting treatments (48 h) with moderate concentrations (3 mu M) elicited junctional uncoupling and impeded the in vitro differentiation of human trophoblasts.