文章基本信息

标题：Role of Calcium/Calmodulin in Cisplatin-Induced Activation of Murine Bone Marrow-Derived Macrophages
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作者：Shishir SHISHODIA ; Ajit SODHI ; Anju SHRIVASTAVA 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：1998
卷号：24
期号：1
页码：1-12
DOI：10.3164/jcbn.24.1
出版社：The Society for Free Radical Research Japan
摘要：In this study we report that the activation of murine bone marrow-derived macrophages (BMDM) to the tumoricidal state by cisplatin is a Ca²⁺- and calmodulin-dependent process. Cisplatin induced an increase in [Ca²⁺]_i in fura-2/AM-loaded BMDM in a cisplatin concentration-dependent manner, as evidenced by progressive increase in the relative fluorescence of the treated cells. Cisplatin-treated BMDM also showed a gradual increase in their ATP level in a cisplatin concentrationdependent manner. There was marked down-regulation of intracellular calcium level when the macrophages were pretreated with pertussis toxin or genistein and subsequently challenged with cisplatin; whereas macrophages treated with cholera toxin showed a slight increase in intracellular calcium, which was significantly upregulated upon cisplatin treatment. Calcium-modulating agents EGTA, nifedipine, and TMB-8, and the calmodulin antagonist W-7, inhibited cisplatin-induced tumoricidal activity of murine BMDM. Supernatants collected from macrophages treated with cisplatin and EGTA, nifedipine, TMB-8, or W-7 demonstrated decreased TNF and IL-1 activity in comparison to supernatants collected from macrophages treated with cisplatin alone.
关键词：cisplatin;Ca2+;macrophages;IL-1;TNF