Essential role of Ca2+-dependent phospholipase A2 in estradiol-induced lysosome activation
Essential role of Ca2+-dependent phospholipase A2 in estradiol-induced lysosome activation
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DOI：
10.1152/ajpcell.00429.2001
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发表时间：
2002-11-01
影响因子：
5.5
通讯作者：
Viarengo, A
中科院分区：
文献类型：
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作者：
Burlando, B;Marchi, B;Viarengo, A
17β-雌二醇激活溶酶体的机制已在贻贝血细胞中进行了研究。用雌二醇处理细胞可诱导胞质游离 Ca2+ 持续增加，但通过将细胞与 Ca2+ 螯合剂 BAPTA-AM 预孵育可完全阻止这种增加。雌二醇处理后还导致溶酶体膜不稳定，如溶酶体对中性红的渗透性增加所检测到的。雌二醇对溶酶体的影响几乎可以通过与胞质 Ca2+ 依赖性 PLA(2) (cPLA(2)) 抑制剂、花生四烯基三氟甲基酮 (AACOCF3) 预孵育而被完全阻止，并且通过与 BAPTA-AM 预孵育而显着降低。相比之下，它几乎不受与 Ca2+ 独立的 PLA(2), (E)-6-(溴亚甲基) 四氢-3-(1-萘基)-2H-吡喃-2-酮 (BEL) 抑制剂预孵育的影响。 Ca2+ 离子载体 A-23187 对 [Ca2+](i) 和溶酶体产生类似的影响。暴露于雌二醇还导致cPLA(2)从细胞质易位至细胞膜、溶酶体增大以及蛋白质降解增加。这些结果表明，细胞暴露于雌二醇后溶酶体膜的不稳定主要通过Ca2+依赖性机制发生，涉及Ca2+依赖性PLA(2)的激活。这种机制促进溶酶体融合和分解代谢活动，并可能介导短期雌二醇效应。
The mechanism of lysosome activation by 17beta-estradiol has been studied in mussel blood cells. Cell treatment with estradiol induced a sustained increase of cytosolic free Ca2+ that was completely prevented by preincubating the cells with the Ca2+ chelator BAPTA-AM. Estradiol treatment was also followed by destabilization of the lysosomal membranes, as detected in terms of the lysosomes' increased permeability to neutral red. The effect of estradiol on lysosomes was almost completely prevented by preincubation with the inhibitor of cytosolic Ca2+-dependent PLA(2) (cPLA(2)), arachidonyl trifluoromethyl ketone (AACOCF3), and was significantly reduced by preincubation with BAPTA-AM. In contrast, it was virtually unaffected by preincubation with the inhibitor of Ca2+ independent PLA(2), (E)-6-(bromomethylene) tetrahydro-3-(1-naphtalenyl)-2H-pyran-2-one (BEL). The Ca2+ ionophore A-23187 yielded similar effects on [Ca2+](i) and lysosomes. Exposure to estradiol also resulted in cPLA(2) translocation from cytosol to membranes, lysosome enlargement, and increased protein degradation. These results suggest that the destabilization of lysosomal membranes following cell exposure to estradiol occurs mainly through a Ca2+-dependent mechanism involving activation of Ca2+-dependent PLA(2). This mechanism promotes lysosome fusion and catabolic activities and may mediate short-term estradiol effects.