CERAMIDE TRIGGERS MEIOTIC CELL-CYCLE PROGRESSION IN XENOPUS OOCYTES - A POTENTIAL MEDIATOR OF PROGESTERONE-INDUCED MATURATION
CERAMIDE TRIGGERS MEIOTIC CELL-CYCLE PROGRESSION IN XENOPUS OOCYTES - A POTENTIAL MEDIATOR OF PROGESTERONE-INDUCED MATURATION
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DOI：
10.1074/jbc.270.22.13541
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发表时间：
1995-06-02
影响因子：
4.8
通讯作者：
BELL, RM
中科院分区：
文献类型：
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作者：
STRUM, JC;SWENSON, KI;BELL, RM
研究了鞘磷脂衍生的第二信使在黄体酮诱导的非洲爪蟾卵母细胞减数分裂细胞周期重新启动中的作用。用鞘磷脂酶（金黄色葡萄球菌）对去卵泡卵母细胞进行简单处理足以诱导成熟，这通过H1激酶活性和生殖囊泡破裂（GVBD）来测量。放线菌酮预处理抑制鞘磷脂酶诱导的GVBD表现出蛋白质合成的要求。神经酰胺或鞘氨醇，鞘磷脂水解的潜在产物，微量注射，能够诱导GVBD在激素的情况下。代谢标记研究表明鞘氨醇转化为神经酰胺是鞘氨醇诱导GVBD所必需的。此外，伏马菌素B（1），鞘氨醇N-酰基转移酶抑制剂，阻断鞘氨醇诱导的GVBD，表明神经酰胺是更接近的生物活性代谢产物。用孕酮（卵母细胞成熟的生理诱导剂）处理卵母细胞导致神经酰胺质量的时间和浓度依赖性增加，并通过激活Mg 2+依赖性中性鞘磷脂酶减少鞘磷脂质量。这些观察结果表明，神经酰胺从鞘磷脂的生成是响应孕酮激活的信号转导途径的一部分，神经酰胺的增加可能在减数分裂细胞周期的恢复中具有重要的功能。
The role of sphingomyelin-derived second messengers in progesterone-induced reinitiation of the meiotic cell cycle of Xenopus laevis oocytes was investigated. A brief treatment of defolliculated oocytes with sphingomyelinase (Staphylococcus aureus) was sufficient to induce maturation as measured by H1 kinase activity and germinal vesicle breakdown (GVBD). Pretreatment with cycloheximide inhibited sphingomyelinase-induced GVBD demonstrating a requirement for protein synthesis. Microinjection of ceramide or sphingosine, potential products of sphingomyelin hydrolysis, were capable of inducing GVBD in the absence of hormone. Metabolic labeling studies suggested the conversion of sphingosine to ceramide was necessary for sphingosine-induced GVBD. Additionally, fumonisin b(1), an inhibitor of sphingosine N-acyltransferase, blocked sphingosine-induced GVBD demonstrating that ceramide is the more proximal biologically active metabolite. Treatment of oocytes with progesterone, the physiological inducer of oocyte maturation, resulted in a time- and concentration-dependent increase in the mass of ceramide and decrease in the mass of sphingomyelin through activation of a Mg2+-dependent neutral sphingomyelinase. These observations suggest that the generation of ceramide from sphingomyelin is part of the signal transduction pathway activated in response to progesterone and that the increase in ceramide is likely to be functionally important in resumption of the meiotic cell cycle.