Ferreira-Silva Valéria, Rodrigues Alice Cristina, Hirata Thiago Dominguez Crespo, Hirabara Sandro Massao, Curi Rui
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Sao Paulo, Brazil.
Eur J Pharmacol. 2008 Feb 2;580(1-2):80-6. doi: 10.1016/j.ejphar.2007.11.004. Epub 2007 Nov 17.
The role of PPARgamma in ciglitazone and 15-d PGJ(2)-induced apoptosis and cell cycle arrest of Jurkat (before and after PPARgamma gene silencing), U937 (express high levels of PPARgamma) and HeLa (that express very low levels of PPARgamma) cells was investigated. PPARgamma gene silencing, per se, induced a G2/M cell arrest, loss of membrane integrity and DNA fragmentation of Jurkat cells, indicating that PPARgamma is important for this cell survival and proliferation. Ciglitazone-induced apoptosis was abolished after knockdown of PPARgamma suggesting a PPARgamma-dependent pro-apoptotic effect. However, ciglitazone treatment was toxic for U937 and HeLa cells regardless of the presence of PPARgamma. This treatment did not change the cell cycle distribution corroborating with a PPARgamma-independent mechanism. On the other hand, 15-d PGJ(2) induced apoptosis of the three cancer cell lines regardless of the expression of PPARgamma. These results suggest that PPARgamma plays an important role for death of malignant T lymphocytes (Jurkat cells) and PPARgamma agonists exert their effects through PPARgamma-dependent and -independent mechanisms depending on the drug and the cell type.
研究了PPARγ在噻唑烷二酮和15 - 脱氧前列腺素J2（15-d PGJ(2)）诱导的Jurkat细胞（PPARγ基因沉默前后）、U937细胞（高表达PPARγ）和HeLa细胞（低表达PPARγ）凋亡及细胞周期阻滞中的作用。PPARγ基因沉默本身可诱导Jurkat细胞出现G2/M期细胞阻滞、膜完整性丧失和DNA片段化，表明PPARγ对该细胞的存活和增殖很重要。PPARγ敲低后，噻唑烷二酮诱导的凋亡被消除，提示存在PPARγ依赖性促凋亡作用。然而，无论PPARγ是否存在，噻唑烷二酮处理对U937和HeLa细胞均有毒性。这种处理并未改变细胞周期分布，证实其作用机制不依赖于PPARγ。另一方面，无论PPARγ表达如何，15-d PGJ(2)均可诱导这三种癌细胞系凋亡。这些结果表明，PPARγ在恶性T淋巴细胞（Jurkat细胞）死亡中起重要作用，并且PPARγ激动剂根据药物和细胞类型通过PPARγ依赖性和非依赖性机制发挥作用。
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