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

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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.

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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

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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.

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  1. Huijie Wang and Feng Niu contributed equally to this work.

Authors and Affiliations

  1. Department of Histology& Embryology, Basic Medicine School, Dali University, Yunnan, China

    Huijie Wang

  2. Department of Rehabilitation, Jinshan Hospital, Fudan University, Shanghai, China

    Feng Niu

  3. Central Laboratory, Jinshan Hospital, Fudan University, No.1508, Longhang Road, Jinshan district, Shanghai, 201508, China

    Wei Fan, Jimin Shi, Jihong Zhang & Bing Li

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  1. Huijie Wang
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  2. Feng Niu
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  3. Wei Fan
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Correspondence to Bing Li.

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Wang, H., Niu, F., Fan, W. et al. Modulating effects of preconditioning exercise in the expression of ET-1 and BNP via HIF-1α in ischemically injured brain. Metab Brain Dis 34, 1299–1311 (2019). https://doi.org/10.1007/s11011-019-00450-z

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