Article Data

  • Views 2045
  • Dowloads 155

Original Research

Open Access

Isoflurane ameliorates oxygen-glucose deprivation-induced cardiomyocyte injury through SIRT6/DNMT1 pathway

  • Qian Wu1
  • Bangshu Zhao1,*,

1The Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China

DOI: 10.22514/sv.2023.020 Vol.19,Issue 2,March 2023 pp.154-160

Submitted: 16 December 2022 Accepted: 01 February 2023

Published: 08 March 2023

*Corresponding Author(s): Bangshu Zhao E-mail: zbs166@163.com

Abstract

The incidence of cardiovascular diseases is on the rise in the world, which poses a significant threat to human health. Myocardial ischemia can cause heart disease. Therefore, it is necessary to avoid myocardial hypoxia/reoxygenation (H/R) injury to attenuate the risk of heart disease. The present study focuses on the protective effect of isoflurane on H/R-induced cell injury through the Sirtuin 6 (SIRT6)/DNA (cytosine-5)-methyltransferase 1 (DNMT1) pathway. Quantitative reverse transcription PCR (RT‑qPCR) and Western blot analysis were used to measure protein levels and mRNA expression in H9c2 cells. Cell Counting Kit‑8 assays (CCK8 assay) was used to determine cell viability. The expression levels of pro-inflammatory molecule were assessed using commercial Enzyme-linked immunosorbent assay (ELISA) Kits. The ratio of cellular apoptosis was determined by flow cytometry. The contents of Lactate dehydrogenase (LDH), Cardiac Troponin I (cTnI), and Creatine Kinase MB (CK-MB) were detected using colorimetric assays. This study shows that Isoflurane reduces the expression of DNMT1 by activating SIRT6 in oxygen-glucose deprivation (OGD)-induced H/R injury. The damage of cardiomyocyte was decreased after Isoflurane treatment under OGD exposure condition. In addition, Isoflurane ameliorates OGD-induced inflammatory responses and cellular apoptosis in H9c2 cell via interaction with the SIRT6/DNMT1 pathway. Taken together, this study suggested the protective effect of Isoflurane on the process of OGD-induced damage and provided a new mechanism of action for Isoflurane in the treatment of H/R-induced cardiomyocyte injury.


Keywords

Isoflurane; OGD; SIRT6; DNMT1; Hypoxia/reoxygenation


Cite and Share

Qian Wu,Bangshu Zhao. Isoflurane ameliorates oxygen-glucose deprivation-induced cardiomyocyte injury through SIRT6/DNMT1 pathway. Signa Vitae. 2023. 19(2);154-160.

References

[1] Thomas H, Diamond J, Vieco A, Chaudhuri S, Shinnar E, Cromer S, et al. Global atlas of cardiovascular disease. Global Heart. 2018; 13: 143–163.

[2] Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, AlKatheeri R, et al. Global epidemiology of ischemic heart disease: results from the global burden of disease study. Cureus. 2020; 12: e9349.

[3] Wei H, Liang G, Yang H. Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity. Neuroscience Letters. 2007; 425: 59–62.

[4] Constantinides C, Mean R, Janssen BJ. Effects of isoflurane anes-thesia on the cardiovascular function of the C57BL/6 mouse. ILAR Journal/National Research Council, Institute of Laboratory Animal Resources. 2011; 52: e21–e31.

[5] Liu J, Yang S, Zhang X, Liu G, Yue X. Isoflurane reduces oxygen-glucose deprivation-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes. American Journal of Translational Research. 2016; 8: 2597.

[6] Su Y, Chen G, Zhang F, Wang L, Feng Z, Gao X. Isoflurane alleviates myocardial injury induced by hypoxia/reoxygenation by regulating miR-18a-5p. Cardiovascular Toxicology. 2021; 21: 800–807.

[7] Trapp J. The role of NAD+ dependent histone deacetylases (sirtuins) in ageing. Current Drug Targets. 2006; 7: 1553–1560.

[8] Mendes KL, de Farias Lelis D, Santos SHS. Nuclear sirtuins and inflammatory signaling pathways. Cytokine & Growth Factor Reviews. 2017; 38: 98–105.

[9] Poulose N, Raju R. Sirtuin regulation in aging and injury. Biochimica Et Biophysica Acta (BBA)—Molecular Basis of Disease. 2015; 1852: 2442–2455.

[10] Tennen RI, Chua KF. Chromatin regulation and genome maintenance by mammalian SIRT6. Trends in Biochemical Sciences. 2011; 36: 39–46.

[11] Wang X, Wang X, Tong M, Gan L, Chen H, Wu S, et al. SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Research in Cardiology. 2016; 111: 13.

[12] Chen G, Zhang F, Wang L, Feng Z. Isoflurane alleviates hypoxia/reoxygenation induced myocardial injury by reducing miR-744 mediated SIRT6. Toxicology Mechanisms and Methods. 2022; 32: 235–242.

[13] Deng Z, Yao J, Xiao N, Han Y, Wu X, Ci C, et al. DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis. Laboratory Investigation. 2022; 102: 782–793.

[14] Boovarahan SR, Kurian GA. Investigating the role of DNMT1 gene expression on myocardial ischemia reperfusion injury in rat and associated changes in mitochondria. Biochimica Et Biophysica Acta (BBA)—Bioenergetics. 2022; 1863: 148566.

[15] Jia B, Chen J, Wang Q, Sun X, Han J, Guastaldi F, et al. SIRT6 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells through antagonizing DNMT1. Frontiers in Cell and Developmental Biology. 2021; 9: 648627.

[16] Bagheri F, Khori V, Alizadeh AM, Khalighfard S, Khodayari S, Khodayari H. Reactive oxygen species-mediated cardiac-reperfusion injury: mechanisms and therapies. Life Sciences. 2016; 165: 43–55.

[17] Zare MFR, Rakhshan K, Aboutaleb N, Nikbakht F, Naderi N, Bakhshesh M, et al. Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats. Life Sciences. 2019; 232: 116623.

[18] Qiu Z, Lei S, Zhao B, Wu Y, Su W, Liu M, et al. NLRP3 inflammasome activation-mediated pyroptosis aggravates myocardial ischemia/reperfusion injury in diabetic rats. Oxidative Medicine and Cellular Longevity. 2017; 2017: 1–17.

[19] Kanazawa M, Miura M, Toriyabe M, Koyama M, Hatakeyama M, Ishikawa M, et al. Microglia preconditioned by oxygen-glucose depri-vation promote functional recovery in ischemic rats. Scientific Reports. 2017; 7: 1–16.

[20] Kurian GA, Rajagopal R, Vedantham S, Rajesh M. The role of oxidative stress in myocardial ischemia and reperfusion injury and remodeling: revisited. Oxidative Medicine and Cellular Longevity. 2016; 2016: 1–14.

[21] Li C, Miao X, Li F, Adhikari BK, Liu Y, Sun J, et al. Curcuminoids: implication for inflammation and oxidative stress in cardiovascular diseases. Phytotherapy Research. 2019; 33: 1302–1317.

[22] Relja B, Land WG. Damage-associated molecular patterns in trauma. European Journal of Trauma and Emergency Surgery. 2020; 46: 751–775.

[23] Anselmi A. Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: a review of evidence. European Journal of Cardio-Thoracic Surgery. 2004; 25: 304–311.

[24] Olson JM, Yan Y, Bai X, Ge Z, Liang M, Kriegel AJ, et al. Up-regulation of MicroRNA-21 mediates isoflurane-induced protection of cardiomyocytes. Anesthesiology. 2015; 122: 795–805.

[25] Sayed S, Idriss NK, Sayyed HG, Ashry AA, Rafatt DM, Mohamed AO, et al. Effects of propofol and isoflurane on haemodynamics and the inflammatory response in cardiopulmonary bypass surgery. British Journal of Biomedical Science. 2015; 72: 93–101.

[26] Zhang S, Zhang Y. Isoflurane reduces endotoxin-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes. European Review for Medical and Pharmacological Sciences. 2018; 22: 3976–3987.

[27] Wei H, Kang B, Wei W, Liang G, Meng QC, Li Y, et al. Isoflurane and sevoflurane affect cell survival and BCL-2/BAX ratio differently. Brain Research. 2005; 1037: 139–147.

[28] Jamnicki-Abegg M, Weihrauch D, Pagel P, Kersten J, Bosnjak Z, Warltier D, et al. Isoflurane inhibits cardiac myocyte apoptosis during oxidative and inflammatory stress by activating akt and enhancing Bcl-2 expression. Anesthesiology. 2005; 103: 1006–1014.

[29] Yang Y, Tian T, Wang Y, Li Z, Xing K, Tian G. SIRT6 protects vascular endothelial cells from angiotensin II-induced apoptosis and oxidative stress by promoting the activation of Nrf2/ARE signaling. European Journal of Pharmacology. 2019; 859: 172516.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.3 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

Top