title: Cumulated Ca2⁺ spike duration underlies Ca2⁺ oscillation frequency-regulated NFκB transcriptional activity.
abstract: [Ca(2+)](i) oscillations drive downstream events, like transcription, in a frequency-dependent manner. Why [Ca(2+)](i) oscillation frequency regulates transcription has not been clearly revealed. A variation in [Ca(2+)](i) oscillation frequency apparently leads to a variation in the time duration of cumulated [Ca(2+)](i) elevations or cumulated [Ca(2+)](i) spike duration. By manipulating [Ca(2+)](i) spike duration, we generated a series of [Ca(2+)](i) oscillations with the same frequency but different cumulated [Ca(2+)](i) spike durations, as well as [Ca(2+)](i) oscillations with the different frequencies but the same cumulated [Ca(2+)](i) spike duration. Molecular assays demonstrated that, when generated in 'artificial' models alone, under physiologically simulated conditions or repetitive pulses of agonist exposure, [Ca(2+)](i) oscillation regulates NFκB transcriptional activity, phosphorylation of IκBα and Ca(2+)-dependent gene expression all in a way actually dependent on cumulated [Ca(2+)](i) spike duration whether or not frequency varies. This study underlines that [Ca(2+)](i) oscillation frequency regulates NFκB transcriptional activity through cumulated [Ca(2+)](i) spike-duration-mediated IκBα phosphorylation.
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.forename: Yubo
authors.initials: Y
authors.lastname: Pi
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Weibin
authors.initials: W
authors.lastname: She
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Yuan
authors.initials: Y
authors.lastname: Su
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002118:Calcium