The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells

  • Kim, Mi-Kyoung (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Park, Hyun-Joo (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Kim, Su-Ryun (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Choi, Yoon Kyung (Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School) ;
  • Bae, Soo-Kyung (Department of Dental Pharmacology, School of Dentistry, Pusan National University) ;
  • Bae, Moon-Kyoung (Department of Oral Physiology, School of Dentistry, Pusan National University)
  • Received : 2015.01.23
  • Accepted : 2015.04.23
  • Published : 2015.07.01
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Abstract

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin- A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.

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References

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