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Prospect of thioredoxin as a possibly effective tool to combat OSAHS

  • Sleep Breathing Physiology and Disorders • Review
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Abstract

Purpose

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is characterized by recurrent upper airway disturbances during sleep leading to episodes of hypopnea or apnea, followed by hypoxemia and subsequent reoxygenation. It is believed that this reoxygenation/reperfusion stage leads to oxidative stress, which then leads to inflammation and cardiovascular diseases. The treatments of patient with OSAHS include surgical and non-surgical therapies with various side effects and common complaints. Therefore, it is important to develop a new, safe, and effective therapeutic treatment. As a small-molecule multifunctional protein, thioredoxin (TRX) has antioxidant and redox regulatory functions at the active site Cys-Gly-Pro. TRX prevents inflammation by suppressing the production of pro-inflammatory cytokines rather than suppressing the immune response.

Methods

We review the papers on the pathophysiological process of OSAHS and the antioxidative and anti-inflammatory effects of TRX.

Results

TRX may play a role in OSAHS by scavenging ROS, blocking the production of inflammatory cytokines, inhibiting the migration and activation of neutrophils, and controlling the activation of ROS-dependent inflammatory signals by regulating the redox state of intracellular target particles. Furthermore, TRX regulates the synthesis, stability, and activity of hypoxia-inducible factor 1 (HIF-1). TRX also has an inhibitory effect on endoplasmic reticulum- and mitochondria-induced apoptosis by regulating the expression of BAX, BCL2, p53, and ASK1.

Conclusion

Understanding the function of TRX may be useful for the treatment of OSAHS.

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Data availability

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Abbreviations

OSAHS :

The characteristic of obstructive sleep apnea–hypopnea syndrome

ROS :

Reactive oxygen species

TRX :

Thioredoxin

HIF-1 :

Hypoxia-inducible factor 1

BAX :

BCL2-associated X

BCL2 :

B-cell lymphoma-2

ASK1 :

Apoptosis signal-regulating kinase 1

NF-κB :

Nuclear factor-κB

CRP :

C-reactive protein

CPAP :

Continuous positive airway pressure

TRXR :

Thioredoxin reductase

NADPH :

Nicotinamide adenine dinucleotide phosphoric acid

IH :

Intermittent hypoxia

TCA :

Tricarboxylic acid

MAPK :

Mitogen-activated protein kinases

AP-1 :

Activated protein-1

GATA 4 :

Globin transcription factor 4

LPS :

Lipopolysaccharide

GSH :

Glutathione

ER :

Endoplasmic reticulum

UPR :

Unfolded protein response

IRE1 :

Inositol-requiring protein-1

PERK :

Protein kinase RNA-like ER kinase

ATF6 :

Activating transcription factor-6

CHOP :

C/EBP homologous protein

MAPKKK :

Mitogen-activated protein kinase kinase kinase

JNK :

C-Jun N-terminal kinase

MAP2Ks :

mitogen-activated protein kinase kinases

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Acknowledgements

We deeply appreciate Kiichi Hirota for guiding us in our writing process extensively.

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Author notes

  1. Ye Pan and You Lu contributed equally to this work.

Authors and Affiliations

  1. Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China

    Ye Pan, You Lu, Jie-dong Zhou, Cui-xue Wang, Jin-quan Wang & Hai Tian

  2. Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan

    Atsushi Fukunaga

  3. Laboratory of Infection and Prevention, Department of Biological Response, Institute for Virus Research, Kyoto University, Kyoto, Japan

    Junji Yodoi

  4. Jiaozhimei Biotechnology, CO, Ltd., Shaoxing, China

    Hai Tian

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  1. Ye Pan
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Contributions

Ye Pan and You Lu: conceptualization, formal analysis, investigation, software, writing—original draft.

Jie-dong Zhou: formal analysis, investigation, methodology, writing—review & editing

Cui-xue Wang, Jin-quan Wang, Atsushi Fukunaga: methodology, writing—review & editing

Junji Yodoi: formal analysis, investigation, writing—review & editing

Hai Tian: data curation, formal analysis, investigation, validation, visualization, writing—review & editing

All authors have read and agreed to publish the final version of the manuscript.

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Correspondence to Hai Tian.

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Pan, Y., Lu, Y., Zhou, Jd. et al. Prospect of thioredoxin as a possibly effective tool to combat OSAHS. Sleep Breath 27, 421–429 (2023). https://doi.org/10.1007/s11325-022-02640-z

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