Liu J, Lee P, Galbiati F, Kitsis R N, Lisanti M P
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Am J Physiol Cell Physiol. 2001 Apr;280(4):C823-35. doi: 10.1152/ajpcell.2001.280.4.C823.
The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.
小窝蛋白-1在细胞凋亡中的潜在作用仍存在争议。在此，我们使用一种明确的反义方法来研究小窝蛋白-1的表达是促凋亡还是抗凋亡。我们发现，携带小窝蛋白-1反义序列的NIH/3T3细胞对星形孢菌素诱导的细胞凋亡具有抗性，这是通过细胞形态、DNA含量、半胱天冬酶3激活和粘着斑激酶裂解来评估的。重要的是，当小窝蛋白-1水平恢复时，细胞对凋亡的敏感性也得以恢复。相反，在T24膀胱癌细胞中重组稳定表达小窝蛋白-1会使这些细胞对半胱天冬酶3激活敏感。与使用NIH/3T3细胞的观察结果一致，T24细胞中小窝蛋白-1的下调会显著降低半胱天冬酶3样活性。使用LY-294002抑制磷脂酰肌醇3激酶途径可恢复对凋亡刺激的敏感性丧失，这提示了小窝蛋白-1产生致敏作用的一种可能机制。因此，我们的结果表明，小窝蛋白-1可能在成纤维细胞（NIH/3T3）和上皮细胞（T24）的凋亡性细胞死亡信号传导中充当偶联或致敏因子。
