Cyclic AMP-specific phosphodiesterase inhibitor rolipram and RO-20-1724 promoted apoptosis in HL60 promyelocytic leukemic cells via cyclic AMP-independent mechanism.
Cyclic AMP-specific phosphodiesterase inhibitor rolipram and RO-20-1724 promoted apoptosis in HL60 promyelocytic leukemic cells via cyclic AMP-independent mechanism.
复制标题
环AMP特异性磷酸二酯酶抑制剂咯利普兰和RO-20-1724通过环AMP独立机制促进HL60早幼粒细胞白血病细胞凋亡。
DOI：
10.1016/s0024-3205(98)00270-7
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发表时间：
1998
期刊：
影响因子：
6.1
通讯作者：
Omburo,GA
中科院分区：
文献类型：
--
作者：
Zhu,WH;Majluf-Cruz,A;Omburo,GA
磷酸二酯酶（PDE）负责cAMP和cGMP的水解，cAMP和cGMP在多种细胞功能中充当细胞内第二信使。在本文中，我们报告了PDE 3和PDE 4是HL 60细胞中表达的两种主要类型的PDE。研究了PDE特异性抑制剂对HL 60细胞凋亡的影响。非特异性抑制剂IBMX和PDE 3特异性抑制剂（米力农和曲喹辛）不促进细胞凋亡。它们抑制紫杉醇或毒胡萝卜素诱导的细胞凋亡。然而，PDE 4特异性抑制剂（咯利普兰和RO-20-1724）在5 h内促进细胞凋亡。在HL 60细胞中，其他cAMP诱导剂（8-溴-cAMP，Sp-cAMP和forskolin）也抑制凋亡，而细胞渗透性cGMP类似物不影响凋亡。因此，IBMX和PDE 3特异性抑制剂可能通过增加细胞内cAMP而防止HL 60细胞凋亡。然而，PDE 4特异性抑制剂诱导的细胞凋亡不太可能是由于cAMP水平增加。这些结果表明咯利普兰和RO-20-1724通过cAMP非依赖性机制促进HL 60细胞凋亡。
Phosphodiesterases (PDEs) are responsible for the hydrolysis of cAMP and cGMP which act as intracellular second messengers in a variety of cellular functions. In this paper we report that PDE3 and PDE4 were two dominant classes of PDEs expressed in HL60 cells. The influence of specific PDE inhibitors on apoptosis in HL60 cells was studied. The non-specific inhibitor IBMX and PDE3 specific inhibitors (milrinone and trequinsin) did not promote apoptosis. They inhibited apoptosis induced by paclitaxel or thapsigargin. However, PDE4 specific inhibitors (rolipram and RO-20-1724) promoted apoptosis within 5 h. In HL60 cells, other cAMP-eliciting reagents (8-bromo-cAMP, Sp-cAMP and forskolin) also inhibited apoptosis, while cell-permeable cGMP analogs did not affect apoptosis. Therefore, IBMX and PDE3 specific inhibitors may prevent HL60 cells from apoptosis by increasing intracellular cAMP. However, apoptosis induced by PDE4 specific inhibitors is not likely due to increased cAMP level. These results suggest that rolipram and RO-20-1724 promoted apoptosis in HL60 cells through cAMP-independent mechanism.