Cumulated Ca2+ spike duration underlies Ca2+ oscillation frequency-regulated NFκB transcriptional activity

被引:42
作者
Zhu, Liping [1 ,2 ]
Song, Shanshan [1 ,2 ]
Pi, Yubo [1 ,2 ]
Yu, Yang [1 ,2 ]
She, Weibin [1 ,2 ]
Ye, Hong [1 ,2 ]
Su, Yuan [2 ,3 ]
Hu, Qinghua [1 ,2 ,4 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Pathophysiol, Tongji Med Coll, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Key Lab Pulm Dis, Minist Hlth China, Wuhan 430030, Peoples R China
[3] Huazhong Univ Sci & Technol, Dept Resp Med, Tongji Med Coll, Union Hosp, Wuhan 430030, Peoples R China
[4] Huazhong Univ Sci & Technol, MOE Key Lab Environm & Hlth, Sch Publ Hlth, Tongji Med Coll, Wuhan 430030, Peoples R China
基金
中国国家自然科学基金;
关键词
Ca2+](i) oscillations; Frequency; Spike duration; Transcription; PROTEIN-KINASE-C; BRONCHIAL EPITHELIAL-CELLS; MICROVASCULAR ENDOTHELIAL-CELLS; CALCIUM OSCILLATIONS; GENE-EXPRESSION; PHORBOL ESTER; HETEROLOGOUS DESENSITIZATION; DIFFERENTIAL ACTIVATION; CHROMAFFIN CELLS; NITRIC-OXIDE;
D O I
10.1242/jcs.082727
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
[Ca2+](i) oscillations drive downstream events, like transcription, in a frequency-dependent manner. Why [Ca2+](i) oscillation frequency regulates transcription has not been clearly revealed. A variation in [Ca2+](i) oscillation frequency apparently leads to a variation in the time duration of cumulated [Ca2+](i) elevations or cumulated [Ca2+](i) spike duration. By manipulating [Ca2+](i) spike duration, we generated a series of [Ca2+](i) oscillations with the same frequency but different cumulated [Ca2+](i) spike durations, as well as [Ca2+](i) oscillations with the different frequencies but the same cumulated [Ca2+](i) spike duration. Molecular assays demonstrated that, when generated in 'artificial' models alone, under physiologically simulated conditions or repetitive pulses of agonist exposure, [Ca2+](i) oscillation regulates NF kappa B transcriptional activity, phosphorylation of I kappa B alpha and Ca2+-dependent gene expression all in a way actually dependent on cumulated [Ca2+](i) spike duration whether or not frequency varies. This study underlines that [Ca2+](i) oscillation frequency regulates NF kappa B transcriptional activity through cumulated [Ca2+](i) spike-duration-mediated I kappa B alpha phosphorylation.
引用
收藏
页码:2591 / 2601
页数:11
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