Role of PKC-δ activity in glutathione-depleted neuroblastoma cells

被引:46
作者
Domenicotti, C
Marengo, B
Verzola, D
Garibotto, G
Traverso, N
Patriarca, S
Maloberti, G
Cottalasso, D
Poli, G
Passalacqua, M
Melloni, E
Pronzato, MA
Marinari, UM
机构
[1] Univ Genoa, Sect Gen Pathol, Dept Expt Med, Genoa, Italy
[2] Univ Genoa, Sect Biochem, Dept Expt Med, Genoa, Italy
[3] Univ Genoa, Div Nephrol, Dept Internal Med, Genoa, Italy
[4] Univ Turin, S Luigi Gonzaga Hosp, Dept Clin & Biol Sci, Turin, Italy
关键词
glutathione; L-buthionine-S; R-sulfoximine; reactive oxygen species; protein kinase C; apoptosis; neuroblastoma; free radicals;
D O I
10.1016/S0891-5849(03)00332-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinases C (PKCs) are a family of isoenzymes sensitive to oxidative modifications and involved in the transduction signal pathways that regulate cell growth. As such, they can act as cellular sensors able to intercept intracellular redox changes and promote the primary adaptive cell response. In this study, we have demonstrated that PKC isoforms are specifically influenced by the amount of intracellular glutathione (GSH). The greatest GSH depletion is associated with a maximal reactive oxygen species (ROS) production and accompanied by an increase in the activity of the delta isoform and a concomitant inactivation of a. ROS generation induced early morphological changes in GSH-depleted neuroblastoma cells characterized, at the intracellular level, by the modulation of PKC-delta activity that was involved in the pathway leading to apoptosis. When cells were pretreated with rottlerin, their survival was improved by the ability of this compound to inhibit the activity of PKC-delta and to counteract ROS production. These results define a novel role of PKC-delta in the cell signaling pathway triggered by GSH loss normally associated with many neurodegenerative diseases and clinically employed in the treatment of neuroblastoma. (C) 2003 Elsevier Inc.
引用
收藏
页码:504 / 516
页数:13
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