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The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia

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Cell Stress and Chaperones Aims and scope

Abstract

Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood–brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK.

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Abbreviations

5-HMF:

5-Hydroxymethyl-2-furfural

MAPK:

Mitogen-activated protein kinases

BBB:

Blood–brain barrier

HE:

Hematoxylin and eosin

ERK:

Extracellular signal regulated kinases

JNK:

c-Jun N-terminal kinases

AMS:

Acute mountain sickness

HACE:

High-altitude cerebral edema

HAPE:

High-altitude pulmonary edema

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Acknowledgments

We would like to thank Dr. Ping Liang, the executive editor of Progress in Natural Science and Dr. Ying Wu in Institute of Basic Medical Sciences, for their critical reading of this manuscript. This work was supported by the National Basic Research Program of China (2006CB504100), and the grants of the Natural Sciences Foundation of China (30831160514, 81071066, and 81000856).

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Authors and Affiliations

  1. Department of Neurobiology, Beijing Institute for Neuro-Science, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China

    Ming-Ming Li & Ming Fan

  2. Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, No. 27 Taiping Rd., Beijing, 100850, People’s Republic of China

    Ming-Ming Li, Li-Ying Wu, Tong Zhao, Kui-Wu Wu, Lei Xiong, Ling-Ling Zhu & Ming Fan

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  1. Ming-Ming Li
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  2. Li-Ying Wu
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  3. Tong Zhao
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Correspondence to Ling-Ling Zhu or Ming Fan.

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Ming-Ming Li and Li-Ying Wu contributed equally to this work.

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Li, MM., Wu, LY., Zhao, T. et al. The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia. Cell Stress and Chaperones 16, 529–537 (2011). https://doi.org/10.1007/s12192-011-0264-8

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