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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
  • 101 Downloads

Abstract

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.

Keywords

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

Abbreviations

BNP

Brain natriuretic peptide

ET-1

Enthothelin-1

ELISA

Enzyme linked immunosorbent assay

EPO

Erythropoietin

EP

Exercise preconditioning

GLUT-1

glucose transportor-1

HMECs

Human microvascular endothelial cells

HUVECs

Human umbilical vein endothelial cells

HIF-1α

Hypoxia-inducible factor -1α

HBSs

HIF-1α binding sites

HRE

HIF-1 responsive element

IGF

Insulin-like growth factor

MCAO

Middle cerebral arterial occlusion

NSCs

Neural stem cells

NIPC

Neuronal ischemic preconditioning

NOS

Nitric oxide synthesis

OS

Oxidative stress

NS

Physiological Saline

TTC

Triphenyltetrazolium chloride

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

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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