Article Data

  • Views 315
  • Dowloads 138

Original Research

Open Access

Protective effect of USP22 against paraquat-induced lung injury via activation of SIRT1/NRF2 pathway

  • Qiaosu Xiao1
  • Rui Lu1
  • Chunmei He1
  • Kai Zhou1

1Department of Emergency Intensive Care Unit, the Affiliated Hospital of Southwest Medical University, 646000 Luzhou City, Sichuan Province, China

DOI: 10.22514/sv.2021.077 Vol.17,Issue 3,May 2021 pp.187-195

Submitted: 26 February 2021 Accepted: 31 March 2021

Published: 08 May 2021

*Corresponding Author(s): Kai Zhou E-mail: zhoukai_999@163.com

Abstract

Introduction: The nonselective herbicide Paraquat (PQ) is broadly used in agricultural production. However, PQ has severe toxicity in humans and results in over 90% of death due to lack of effective therapy strategies. Ubiquitin Specific Peptidase 22 (USP22) is a deubiquitinase and it exerts a vital role in regulating ROS production. This study aimed to study the effect of USP22 on PQ-induced lung injury and investigate the precise mechanism.

Methods: The lung injury model was induced by treating with PQ. Hematoxylin and eosin (HE) staining and lung wet/dry ratio were conducted to assess lung tissue injury. Myeloperoxidase (MPO) activity was detected to evaluate neutrophil infiltration in the lung tissues. Superoxidase dismutase (SOD) activity and Malondialdehyde (MDA) content were measured to determine oxidative damage. Cell viability and cell apoptosis were detected using MTT assay and Flow cytometry.

Results: PQ caused lung tissue damage and increased lung wet/dry ratio. PQ increased the MPO activity and MDA content, and decreased SOD activity. USP22 was down-regulated in PQ-treated mice. Besides, overexpression of USP22 alleviated PQ-induced cell apoptosis and oxidative damage in vitro. Furthermore, overexpression of USP22 increased the expression of Sirtuin 1 (SIRT1)/nuclear factor E2-related factor 2 (NRF2). Down-regulation of SIRT1 reversed the beneficial influence of overexpressed USP22 on PQ-induced cell apoptosis and oxidative damage. Moreover, overexpression of USP22 attenuated PQ induced lung injury in vivo.

Conclusions: Overexpression of USP22 alleviated PQ-induced lung injury through activating SIRT1/NRF2 pathway. USP22 may be a valuable target for the treatment of PQ-induced lung injury.


Keywords

Paraquat; Lung injury; USP22; SIRT1; NRF2; Oxidative damage


Cite and Share

Qiaosu Xiao,Rui Lu,Chunmei He,Kai Zhou. Protective effect of USP22 against paraquat-induced lung injury via activation of SIRT1/NRF2 pathway. Signa Vitae. 2021. 17(3);187-195.

References

[1] Zhang Z, Nian Q, Chen G, Cui S, Han Y, Zhang J. Klotho alleviates lung injury caused by paraquat via suppressing ROS/P38 MAPK-regulated inflammatory responses and apoptosis. Oxidative Medicine and Cellular Longevity. 2020; 2020: 1854206.

[2] Yin Y, Guo X, Zhang SL, Sun CY. Analysis of paraquat intoxication epidemic (2002–2011) within China. Biomedical and Environmental Sciences. 2013; 26: 509–512.

[3] Dinis-Oliveira RJ, Duarte JA, Sánchez-Navarro A, Remião F, Bastos ML, Carvalho F. Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Critical Reviews in Toxicology. 2008; 38: 13–71.

[4] Zhang L, Li Q, Liu Z, Liu W, Zhao M. Protective effects of a rho kinase inhibitor on paraquat-induced acute lung injuries in rats. Inflammation. 2018; 41: 2171–2183.

[5] Chen C, Chou H, Hsu H, Wang L. Transforming growth factor-β1 upregulation is independent of angiotensin in paraquat-induced lung fibrosis. Toxicology. 2005; 216: 181–187.

[6] Ren Y, Yang Z, Sun Z, Zhang W, Chen X, Nie S. Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin inter-acting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway. Molecular Medicine Reports. 2019; 20: 5032–5040.

[7] Liu B, Cao B, Zhang D, Xiao N, Chen H, Li G, et al. Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling. Toxicology and Applied Pharmacology. 2016; 309: 111–120.

[8] Tomita M, Okuyama T, Katsuyama H, Miura Y, Nishimura Y, Hidaka K, et al. Mouse model of paraquat-poisoned lungs and its gene expression profile. Toxicology. 2007; 231: 200–209.

[9] Liu Y, Yang Y, Xu H, Dong X. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer. Journal of Surgical Oncology. 2011; 103: 283–289.

[10] Schrecengost RS, Dean JL, Goodwin JF, Schiewer MJ, Urban MW, Stanek TJ, et al. USP22 regulates oncogenic signaling pathways to drive lethal cancer progression. Cancer Research. 2014; 74: 272–286.

[11] Zhang Y, Yao L, Zhang X, Ji H, Wang L, Sun S, et al. Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer. Journal of Cancer Research and Clinical Oncology. 2011; 137: 1245–1253.

[12] Xu J, Tan Q, Li T. USP22 promotes the expression of GLUT1 and HK2 to facilitate growth and glycolysis in cervical cancer cells. European Journal of Gynaecological Oncology. 2020; 41: 790–796.

[13] Ma S, Sun L, Wu W, Wu J, Sun Z, Ren J. USP22 protects against myocardial ischemia—Reperfusion injury via the SIRT1-p53/SLC7A11-dependent inhibition of ferroptosis-induced cardiomyocyte death. Fron-tiers in Physiology. 2020; 11: 551318.

[14] Ji A, Li T, Zu G, Feng D, Li Y, Wang G, et al. Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury. World Journal of Gastroenterology. 2019; 25: 824–836.

[15] Shi J, Wang Q, Li H, Huang Q. Silencing of USP22 suppresses high glucose-induced apoptosis, ROS production and inflammation in podocytes. Molecular BioSystems. 2016; 12: 1445–1456.

[16] Li A, Liu Y, Zhai L, Wang L, Lin Z, Wang S. Activating peroxisome proliferator-activated receptors (PPARs): a new sight for chrysophanol to treat paraquat-induced lung injury. Inflammation. 2016; 39: 928–937.

[17] Tyagi N, Dash D, Singh R. Curcumin inhibits paraquat induced lung inflammation and fibrosis by extracellular matrix modifications in mouse model. Inflammopharmacology. 2016; 24: 335–345.

[18] Jang YJ, Won JH, Back MJ, Fu Z, Jang JM, Ha HC, et al. Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells. Biomolecules & Therapeutics. 2015; 23: 407–413.

[19] Sun D, Song C, Xu Y, Wang R, Liu W, Liu Z, et al. Involvement of PINK1/Parkin-mediated mitophagy in paraquat-induced apoptosis in human lung epithelial-like a549 cells. Toxicology in Vitro. 2018; 53: 148–159.

[20] Park SY, Kim HY, Park HJ, Shin HK, Hong KW, Kim CD. Concurrent treatment with taxifolin and cilostazol on the lowering of β-amyloid accumulation and neurotoxicity via the suppression of P-JAK2/P-STAT3/NF-κB/BACE1 signaling pathways. PLoS ONE. 2016; 11: e0168286.

[21] Lee HR, Shin HK, Park SY, Kim HY, Lee WS, Rhim BY, et al. Atten-uation of β-amyloid-induced tauopathy via activation of CK2α/SIRT1: targeting for cilostazol. Journal of Neuroscience Research. 2014; 92: 206–217.

[22] Ding Y, Zhao G, Li X, Hong G, Li M, Qiu Q, et al. SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro. International Journal of Molecular Medicine. 2016; 37: 1049–1058.

[23] Lin Z, Yang H, Kong Q, Li J, Lee S, Gao B, et al. USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Molecular Cell. 2012; 46: 484–494.

[24] Kumari A, Tyagi N, Dash D, Singh R. Intranasal curcumin ameliorates lipopolysaccharide-induced acute lung injury in mice. Inflammation. 2015; 38: 1103–1112.

[25] An X, Sun X, Hou Y, Yang X, Chen H, Zhang P, et al. Protective effect of oxytocin on LPS-induced acute lung injury in mice. Scientific Reports. 2019; 9: 2836.

[26] Chen Q, Zhang X, Zhao J, Lu X, Zheng P, Xue X. Oxidative damage of the male reproductive system induced by paraquat. Journal of Biochemical and Molecular Toxicology. 2017; 31: e21870.

[27] Shalaby MA, Emam SR, Soliman AM. Protective effect of vitamin e against herbicide paraquat-induced enzymatic leakage and oxidative damage in the liver of rats. Advances in Animal and Veterinary Sciences. 2020; 8: 639–646.

[28] Chang X, Lu W, Dou T, Wang X, Lou D, Sun X, et al. Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells. Chemico-Biological Interactions. 2013; 206: 248–255.

[29] Zerin T, Kim Y, Hong S, Song H. Protective effect of methylprednisolone on paraquat-induced a549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression. Toxicology Letters. 2012; 208: 101–107.

[30] Zhou D, Liu P, Sun D, Chen Z, Hu J, Peng S, et al. USP22 down-regulation facilitates human retinoblastoma cell aging and apoptosis via inhibiting TERT/P53 pathway. European Review for Medical and Pharmacological Sciences. 2017; 21: 2785–2792.

[31] Liu B, Zhang H, Tan X, Yang D, Lv Z, Jiang H, et al. GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney. Oncotarget. 2017; 8: 42226–42237.

[32] Tan X, Liu B, Lu J, Li S, Baiyun R, Lv Y, et al. Dietary luteolin protects against HgCl_2-induced renal injury via activation of Nrf2-mediated signaling in rat. Journal of Inorganic Biochemistry. 2018; 179: 24–31.

[33] Lv Y, Jiang H, Li S, Han B, Liu Y, Yang D, et al. Sulforaphane prevents chromium-induced lung injury in rats via activation of the Akt/GSK-3β/Fyn pathway. Environmental Pollution. 2020; 259: 113812.

[34] Yang D, Lv Z, Zhang H, Liu B, Jiang H, Tan X, et al. Activation of the Nrf2 signaling pathway involving klf9 plays a critical role in allicin resisting against arsenic trioxide-induced hepatotoxicity in rats. Biological Trace Element Research. 2017; 176: 192–200.

[35] Bai X, Fan L, He T, Jia W, Yang L, Zhang J, et al. SIRT1 protects rat lung tissue against severe burn-induced remote ALI by attenuating the apoptosis of PMVECs via p38 MAPK signaling. Scientific Reports. 2015; 5: 10277.

[36] Kim J, Jo J, Kim K, An H, Gwon M, Gu H, et al. Pharmacological activation of SIRT1 ameliorates cisplatin-induced acute kidney injury by suppressing apoptosis, oxidative stress, and inflammation in mice. Antioxidants. 2019; 8: 322.

[37] Han B, Li S, Lv Y, Yang D, Li J, Yang Q, et al. Dietary melatonin attenuates chromium-induced lung injuryviaactivating the Sirt1/Pgc-1α/Nrf2 pathway. Food & Function. 2019; 10: 5555–5565.


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.

IndexCopernicus 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 0.5(2019) 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