Apoptosis and release of CD44s in bleomycin‐treated L132 cells

Apoptosis and release of CD44s in bleomycin‐treated L132 cells
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博莱霉素处理的 L132 细胞中的凋亡和 CD44 释放

DOI:
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发表时间:
2005
影响因子:
4
通讯作者:
M. Kasper
M. Kasper
中科院分区:
生物学2区
文献类型:
--
作者:
R. Koslowski;F. Fichtner;K. Barth;C. Roehlecke;D. Seidel;M. Kasper

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抗癌药物博莱霉素(BLM)可引起肺损伤,并引发肺泡上皮细胞凋亡。在上皮细胞中,黏附蛋白CD44除了其他功能外,还促进与透明质酸等细胞外基质成分的接触。在结肠癌细胞中发现了细胞凋亡与CD44缺失之间的功能联系,一些研究报道了CD44参与了肺细胞的凋亡。本研究在体外检测了BLM诱导的人肺上皮细胞株L132和A549中CD44s(CD44标准)的表达。肺上皮细胞CD44s缺失,培养上清液中CD44s的可溶性含量增加。细胞凋亡的特征是caspase-3的激活以及细胞色素C释放到胞浆中,如L132细胞所示。广谱的caspase抑制剂Z-VAD-fmk抑制细胞凋亡可减少两种细胞CD44的释放,表明CD44的释放是细胞凋亡过程的结果。动力学实验未能区分细胞凋亡的启动和CD44的释放。用拮抗性抗CD95受体抗体阻断实验表明,BLM可能以非CD95依赖的方式引起细胞凋亡和CD44释放。©2005 Wiley-Liss Inc.
The anti‐cancer drug bleomycin (BLM) induces lung injury and triggers apoptosis of alveolar epithelial cells. In epithelia, among other functions, the adhesion protein CD44 promotes the contact to components of the extracellular matrix like hyaluronate. A functional link between apoptosis and the loss of CD44 has been observed in colon carcinoma cells and involvement of CD44 in apoptosis of lung cells has been reported in several studies. The present in vitro study examined the expression of CD44s (CD44 standard) in two human epithelial lung cell lines, L132 and A549, during BLM‐induced apoptosis. A loss of CD44s by lung epithelial cells and an increase of the soluble form of this adhesion protein in culture supernatants upon exposure to BLM were observed. Apoptosis was characterized by an activation of caspase‐3 as well as by release of cytochrome C into the cytosol as shown for L132 cells. Inhibition of apoptosis by the broad‐range caspase inhibitor Z‐VAD‐fmk reduced CD44 release by both cell lines demonstrating that CD44 release is a result of apoptotic processes. Kinetic experiments failed to discriminate between the initiation of apoptosis and CD44 release. Blocking experiments using antagonistic anti‐CD95 receptor antibodies revealed that BLM may cause apoptosis and CD44 release in a CD95‐independent manner. © 2005 Wiley‐Liss, Inc.
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