Redox control of G(1)/S cell cycle regulators during nitric oxide-mediated cell cycle arrest.
Redox control of G(1)/S cell cycle regulators during nitric oxide-mediated cell cycle arrest.
复制标题
一氧化氮介导的细胞周期停滞期间 G(1)/S 细胞周期调节剂的氧化还原控制。
DOI：
10.1002/jcp.21079
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发表时间：
2007
影响因子：
5.6
通讯作者：
Jourd'Heuil,David
中科院分区：
文献类型：
--
作者：
Lu,Qi;Jourd'Heuil,FrancesL;Jourd'Heuil,David
Redox regulation of cell cycle progression during nitric oxide (NO) mediated cytostasis is not well‐understood. In this study, we investigated the role of the intracellular antioxidant glutathione (GSH) in regulating specific signaling events that are associated with NO‐mediated cell cycle arrest. Manipulation of intracellular GSH content through pharmacological inhibition of glutamate‐cysteine ligase (GCL) indicated that GSH depletion potentiated nitrosative stress, DNA damage, phosphorylation of the tumor suppressor p53 (Ser‐18) and upregulation of p21cip1/waf1upon NO stimulation. However, we found that neither overexpression of a dominant negative p53 nor pharmacological inhibition of p53 with cyclic pifithrin‐α (cPFT‐α) was sufficient to reverse NO‐mediated cell cycle arrest or hypophosphorylation of retinoblastoma protein (Rb). We found that the decrease in cyclin D1 levels induced by NO was GSH‐sensitive implying that the redox regulation of NO‐mediated cytostasis was a multifaceted process and that both p53/p21cip1/waf1and p53 independent cyclin D1 pathways were involved. Together, our results demonstrate that GSH serves as an important component of cellular protective mechanisms against NO‐derived nitrosative stress to regulate DNA damage checkpoint. J. Cell. Physiol. 212:827–839, 2007. © 2007 Wiley‐Liss, Inc.
