Authors: Hui Tian JinXia Wu FengXiao Shan ShangNuan Zhang Qian Cheng JunNian Zheng DongSheng Pei
Publish Date: 2014/09/19
Volume: 71, Issue: 2, Pages: 679-688
Abstract
Gammaaminobutyric acid GABA an inhibitory neurotransmitter in central nervous system has yet been found to widely exist in tumor tissues to regulate tumor cells growth However the function of GABA on inducing tumor cells apoptosis and the potential mechanism are still unclear In order to detect whether GABA via GABAB receptor GABABR1 would activate cJun Nterminal kinases JNKs to promote tumor cells apoptosis coimmunoprecipitation assay was used to investigate the association of βarrestins with GABABR1 and JNKs in the different four cancer cell lines Our observation demonstrated that βarrestins in addition to their role in G proteincoupled receptors desensitization had an additional function as adapter proteins to recruit JNKs to GABABR1 thereby conferring distinct enzymatic activities upon the receptor which may trigger JNKs signal pathway involved in the regulation of cellular growth Activated JNKs subsequently phosphorylated downstream cJun to transcribe a wide variety of proapoptotic genes Additionally GABA upregulated the ratio of proapoptotic protein Bax to antiapoptotic protein Bcl2 and thus facilitated caspase3 cleavage leading to tumor cells apoptosis in a mitochondrialdependent pathway In contrast GABABR antagonist CGP35348 reversed GABAinduced JNKs phosphorylation and its downstream proteins activation which consequently restrained tumor cells apoptosis Taken together our study suggested that GABA via its receptor GABABR1 recruited βarrestins to facilitate the activation of JNKs cascade resulting in tumor cells growth inhibition
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