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首页> 外文期刊>European Journal of Cell Biology: Journal of Deutsche Gesellschaft fur Elektronenmikroskopie: Journal of Deutsche Gesellschaft fur Zellbiologie >Cholesterol regulates prostasome release from secretory lysosomes in PC-3 human prostate cancer cells
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Cholesterol regulates prostasome release from secretory lysosomes in PC-3 human prostate cancer cells

机译:胆固醇调节PC-3人前列腺癌细胞中分泌型溶酶体的前体释放

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摘要

Prostasomes are vesicles secreted by epithelial cells of the prostate gland. However, little is known about the mechanism and the regulation of prostasome secretion. Since endocytic organelles may be involved in prostasome release, PC-3-derived prostasomes were investigated by Western blot analysis for the presence of marker proteins normally associated with these organelles. Prostasomes secreted by PC-3 cells contain clathrin, Tsg101, Hrs, Rab11, Rab5, LAMP-1, LAMP-2, LAMP-3/CD63, and annexin II. Moreover, electron microscopy of PC-3 cells revealed the presence of characteristic multivesicular body-like secretory lysosomes containing vesicles with the same size-distribution as released prostasomes. Ultrastructural immunogold labelling showed that LAMP-1, LAMP-2 and LAMP-3/CD63 were associated with these vesicles. In addition, we have investigated whether cholesterol plays a role in prostasome release by the human prostate cancer cell line PC-3. Interestingly, prostasome release was significantly increased when the cholesterol levels of PC-3 cells were reduced by the cholesterol-sequestering agent methyl-beta-cyclodextrin (MBCD), or by treatment with lovastatin and mevalonate. In conclusion, these studies indicate that cholesterol plays an important role in the release of prostasomes by the human prostate cancer PC-3 cells, and suggest that prostasomes may be released after fusion of secretory lysosomes with the plasma membrane.
机译:前体是前列腺腺上皮细胞分泌的囊泡。然而,关于前列腺脂质体分泌的机制和调控知之甚少。由于内吞性细胞器可能参与前体释放,因此通过蛋白质印迹分析研究了PC-3衍生的前体是否存在通常与这些细胞器相关的标记蛋白。 PC-3细胞分泌的前体含有网格蛋白,Tsg101,Hrs,Rab11,Rab5,LAMP-1,LAMP-2,LAMP-3 / CD63和膜联蛋白II。此外,PC-3细胞的电子显微镜检查显示存在特征性的多囊泡状体状分泌溶酶体,该溶酶体包含与释放的前列腺体具有相同大小分布的囊泡。超微结构免疫金标记显示LAMP-1,LAMP-2和LAMP-3 / CD63与这些囊泡有关。另外,我们研究了胆固醇是否在人前列腺癌细胞系PC-3的前体释放中起作用。有趣的是,当胆固醇截留剂甲基-β-环糊精(MBCD)或洛伐他汀和甲羟戊酸治疗降低PC-3细胞的胆固醇水平时,前体释放显着增加。总之,这些研究表明胆固醇在人前列腺癌PC-3细胞释放前体中起着重要作用,并暗示在分泌型溶酶体与质膜融合后,前体可以被释放。

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