Metabolic Brain Disease

, Volume 34, Issue 5, pp 1299–1311 | Cite as

Modulating effects of preconditioning exercise in the expression of ET-1 and BNP via HIF-1α in ischemically injured brain

  • Huijie Wang
  • Feng Niu
  • Wei Fan
  • Jimin Shi
  • Jihong Zhang
  • Bing LiEmail author
Original Article


It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.


Exercise preconditioning Hypoxia-inducible factor -1α (HIF-1α) ET-1 BNP Middle cerebral arterial occlusion (MCAO) 



Brain natriuretic peptide




Enzyme linked immunosorbent assay




Exercise preconditioning


glucose transportor-1


Human microvascular endothelial cells


Human umbilical vein endothelial cells


Hypoxia-inducible factor -1α


HIF-1α binding sites


HIF-1 responsive element


Insulin-like growth factor


Middle cerebral arterial occlusion


Neural stem cells


Neuronal ischemic preconditioning


Nitric oxide synthesis


Oxidative stress


Physiological Saline


Triphenyltetrazolium chloride


Vascular endothelial growth factor



This investigation was supported by grants from the Traditional Chinese Medicine Research Fund of Shanghai Municipal Commission of Health and Family Planning (2012J019A) to YC.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Histology& Embryology, Basic Medicine SchoolDali UniversityYunnanChina
  2. 2.Department of Rehabilitation, Jinshan HospitalFudan UniversityShanghaiChina
  3. 3.Central Laboratory, Jinshan HospitalFudan UniversityShanghaiChina

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