Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells

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• 作者：I-Hui Yang (13) (14)
  Yao-Ting Tsai (13)
  Siou-Jin Chiu (13)
  Li-Teh Liu (11)
  Hsuan-Hung Lee (13)
  Ming-Feng Hou (12) (13)
  Wen-Li Hsu (14)
  Ben-Kuen Chen (11)
  Wei-Chiao Chang (12) (12) (13) (13) (14)
  
• 关键词：STIM1 ; Orai1 ; Store ; operated calcium channel ; Retinal pigment epithelial cell ; Proliferative vitreoretinopathy
• 刊名：Journal of Biomedical Science
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：20
• 期：1
• 全文大小：1,150 KB
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• 作者单位：I-Hui Yang (13) (14)
  Yao-Ting Tsai (13)
  Siou-Jin Chiu (13)
  Li-Teh Liu (11)
  Hsuan-Hung Lee (13)
  Ming-Feng Hou (12) (13)
  Wen-Li Hsu (14)
  Ben-Kuen Chen (11)
  Wei-Chiao Chang (12) (12) (13) (13) (14)
  
  13. Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan
  14. Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
  11. Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan
  12. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
  
• ISSN：1423-0127

文摘

Background In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line). Results EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation. Conclusions Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders.