» Articles » PMID: 35163007

Reduction in Ventilation-Induced Diaphragmatic Mitochondrial Injury Through Hypoxia-Inducible Factor 1α in a Murine Endotoxemia Model

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 Feb 15
PMID 35163007
Authors
Affiliations
Soon will be listed here.
Abstract

Mechanical ventilation (MV) is essential for patients with sepsis-related respiratory failure but can cause ventilator-induced diaphragm dysfunction (VIDD), which involves diaphragmatic myofiber atrophy and contractile inactivity. Mitochondrial DNA, oxidative stress, mitochondrial dynamics, and biogenesis are associated with VIDD. Hypoxia-inducible factor 1α (HIF-1α) is crucial in the modulation of diaphragm immune responses. The mechanism through which HIF-1α and mitochondria affect sepsis-related diaphragm injury is unknown. We hypothesized that MV with or without endotoxin administration would aggravate diaphragmatic and mitochondrial injuries through HIF-1α. C57BL/6 mice, either wild-type or HIF-1α-deficient, were exposed to MV with or without endotoxemia for 8 h. MV with endotoxemia augmented VIDD and mitochondrial damage, which presented as increased oxidative loads, dynamin-related protein 1 level, mitochondrial DNA level, and the expressions of HIF-1α and light chain 3-II. Furthermore, disarrayed myofibrils; disorganized mitochondria; increased autophagosome numbers; and substantially decreased diaphragm contractility, electron transport chain activities, mitofusin 2, mitochondrial transcription factor A, peroxisome proliferator activated receptor-γ coactivator-1α, and prolyl hydroxylase domain 2 were observed ( < 0.05). Endotoxin-stimulated VIDD and mitochondrial injuries were alleviated in HIF-1α-deficient mice ( < 0.05). Our data revealed that endotoxin aggravated MV-induced diaphragmatic dysfunction and mitochondrial damages, partially through the HIF-1α signaling pathway.

Citing Articles

Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models.

Zeng R, Xu H, Wu M, Zhou X, Lei P, Yu J Front Physiol. 2024; 15:1483594.

PMID: 39717825 PMC: 11663891. DOI: 10.3389/fphys.2024.1483594.


Identification of ferroptosis-associated genes and potential pharmacological targets in sepsis-induced myopathy.

Wang D, Xu L, Liu Y, Wang C, Xu Z, Yang F Heliyon. 2024; 10(7):e29062.

PMID: 38601693 PMC: 11004882. DOI: 10.1016/j.heliyon.2024.e29062.


Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.

Ruan H, Zhang Q, Zhang Y, Li S, Ran X Crit Care. 2024; 28(1):100.

PMID: 38539163 PMC: 10976824. DOI: 10.1186/s13054-024-04885-4.


Research progress on the pathogenesis and treatment of ventilator-induced diaphragm dysfunction.

Zhang J, Feng J, Jia J, Wang X, Zhou J, Liu L Heliyon. 2023; 9(11):e22317.

PMID: 38053869 PMC: 10694316. DOI: 10.1016/j.heliyon.2023.e22317.


Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.

DeRuisseau L, Receno C, Cunningham C, Bates M, Goodell M, Liang C Function (Oxf). 2023; 4(6):zqad058.

PMID: 37954975 PMC: 10634617. DOI: 10.1093/function/zqad058.


References
1.
Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R . Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002; 360(9328):219-23. DOI: 10.1016/S0140-6736(02)09459-X. View

2.
Moroz N, Maes K, Leduc-Gaudet J, Goldberg P, Petrof B, Mayaki D . Oxidants Regulated Diaphragm Proteolysis during Mechanical Ventilation in Rats. Anesthesiology. 2019; 131(3):605-618. DOI: 10.1097/ALN.0000000000002837. View

3.
Ow C, Trask-Marino A, Betrie A, Evans R, May C, Lankadeva Y . Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice. J Clin Med. 2021; 10(17). PMC: 8432047. DOI: 10.3390/jcm10173798. View

4.
Yamada T, Dawson T, Yanagawa T, Iijima M, Sesaki H . SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019; 15(11):2012-2018. PMC: 6844492. DOI: 10.1080/15548627.2019.1643185. View

5.
Lu Z, Ge H, Xu L, Guo F, Zhang G, Wu Y . Alterations in diaphragmatic function assessed by ultrasonography in mechanically ventilated patients with sepsis. J Clin Ultrasound. 2019; 47(4):206-211. DOI: 10.1002/jcu.22690. View