Low-Dose Endothelial Monocyte-Activating Polypeptide-II Induces Blood–Tumor Barrier Opening Via the cAMP/PKA/Rac1 Pathway

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• 作者：Zhen Li ; Xiao-bai Liu ; Yun-hui Liu ; Yi-xue Xue…
• 关键词：Endothelial monocyte ; activating polypeptide ; II ; Blood−tumor barrier ; Permeability ; cAMP ; PKA ; Rac1
• 刊名：Journal of Molecular Neuroscience
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：58
• 期：2
• 页码：153-161
• 全文大小：2,155 KB
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• 作者单位：Zhen Li (1)
  Xiao-bai Liu (2)
  Yun-hui Liu (1)
  Yi-xue Xue (3) (4)
  Jing Liu (1)
  Hao Teng (1)
  Zhuo Xi (1)
  Yi-long Yao (1)
  
  1. Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, 110004, People’s Republic of China
  2. The 96th Class, 7-Year Program, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
  3. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
  4. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
  
• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

Previous studies have demonstrated that low-dose endothelial monocyte-activating polypeptide-II (EMAP-II) induces blood–tumor barrier (BTB) hyperpermeability via both paracellular and transcellular pathways. In a recent study, we revealed that cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent signaling pathway is involved in EMAP-II-induced BTB hyperpermeability. This study further investigated the exact mechanisms through which the cAMP/PKA-dependent signaling pathway affects EMAP-II-induced BTB hyperpermeability. In an in vitro BTB model, low-dose EMAP-II (0.05 nM) induced a significant decrease in Rac1 activity in rat brain microvascular endothelial cells (RBMECs). Pretreatment with forskolin to elevate intracellular cAMP concentration completely blocked EMAP-II-induced inactivation of Rac1. Besides, pretreatment with 6Bnz-cAMP to activate PKA partially attenuated EMAP-II-induced Rac1 inactivation. Moreover, 6Bnz-cAMP pretreatment significantly diminished EMAP-II-induced changes in BTB permeability, myosin light chain (MLC) phosphorylation, expression and distribution of ZO-1, and actin cytoskeleton arrangement in RBMECs. These effects of 6Bnz-cAMP were completely blocked in the presence of NSC-23766 (the specific inhibitor of Rac1). In conclusion, this study demonstrates that low-dose EMAP-II induces BTB hyperpermeability via the cAMP/PKA/Rac1 signaling pathway. Keywords Endothelial monocyte-activating polypeptide-II Blood−tumor barrier Permeability cAMP PKA Rac1