Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway

Dongmei Zhu; Lingli Luo; Hanjie Zeng; Zheng Zhang; Min Huang; Suming Zhou

doi:10.7555/JBR.36.20220212

Volume 37 Issue 4

Jul. 2023

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Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research, 2023, 37(4): 290-301. doi: 10.7555/JBR.36.20220212

Citation:

Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research, 2023, 37(4): 290-301. doi: 10.7555/JBR.36.20220212

Citation:

Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research, 2023, 37(4): 290-301. doi: 10.7555/JBR.36.20220212

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Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway

doi: 10.7555/JBR.36.20220212

Department of Geriatrics Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

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Corresponding author: Min Huang and Suming Zhou, Department of Geriatrics Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Tels: +86-25-68305051 and +86-25-68305053, E-mails: hmdoctor@163.com and zhousmco@aliyun.com;
Received: 2022-09-25
Revised: 2022-11-13
Accepted: 2022-11-22

Published: 2023-05-29

Issue Date: 2023-07-28

Abstract

Abstract

Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis, which is associated with high morbidity and mortality. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), encoded by Hsd11b1, is a reductase that can convert inactive cortisone into metabolically active cortisol, but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood. The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide (LPS)-induced mouse model, in which LPS (10 mg/kg) was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice. We asscessed cardiac function by echocardiography, performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes, and determined the levels of reactive oxygen species and biomarkers of oxidative stress. We also employed polymerase chain reaction analysis, Western blotting, and immunofluorescent staining to determine the expression of related genes and proteins. To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction, we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes. We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury, oxidative stress, and inflammation, along with an improved myocardial function; furthermore, the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and silent information regulator 1 (SIRT1) protein levels both in vivo and in vitro. Therefore, the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
- 11β-HSD1,
- LPS,
- sepsis-induced myocardial dysfunction,
- inflammation,
- oxidative stress

CLC number: 542.2, Document code: A
The authors reported no conflict of interests.

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References(26)

References

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