title: Stromal interaction molecule 1 (STIM1) and Orai1 mediate histamine-evoked calcium entry and nuclear factor of activated T-cells (NFAT) signaling in human umbilical vein endothelial cells.
abstract: Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca(2+) mobilization by releasing Ca(2+) from the endoplasmic reticulum and eliciting Ca(2+) entry across the plasma membrane. Herein, we show that histamine-evoked Ca(2+) entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca(2+) release-activated Ca(2+) (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca(2+) entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca(2+) influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca(2+) mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation.
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Zhou
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zheng
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Si
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Jin
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Peng
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, and.
authors.forename: Lian
authors.initials: L
authors.lastname: He
authors.affiliation: From the Departments of Medical Physiology and Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, and.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Materials Science and Biophysics Department, Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Av. Universidad S/N, Col. Chamilpa, 62210 Cuernavaca, Morelos, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Muñoz-Garay
authors.affiliation: From the Departments of Medical Physiology and.
authors.forename: David C
authors.initials: DC
authors.lastname: Zawieja
authors.affiliation: From the Departments of Medical Physiology and Surgery, Baylor Scott & White Health, College of Medicine, Texas A&M Health Science Center, Temple, Texas 76504, lkuo@medicine.tamhsc.edu.
authors.forename: Lih
authors.initials: L
authors.lastname: Kuo
authors.affiliation: From the Departments of Medical Physiology and xpeng@medicine.tamhsc.edu.
authors.forename: Xu
authors.initials: X
authors.lastname: Peng
authors.affiliation: From the Departments of Medical Physiology and shenyuan.zhang@medicine.tamhsc.edu.
authors.forename: Shenyuan L
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020868:Gene Silencing; D006632:Histamine / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D034622:RNA Interference; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D016209:Interleukin-8; D007378:Interleukins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071741:ORAI2 Protein; C514506:ORAI2 protein, human; C522867:Orai3 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D006632:Histamine; D002118:Calcium
keywords: CRAC Channel; Calcium Imaging; Calcium Release-activated Calcium Channel Protein 1 (ORAI1); HUVEC; Histamine; Interleukin; NFAT Transcription Factor; Stromal Interaction Molecule 1 (STIM1)