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Title:
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Harmine Combined with Rad54 Knockdown Inhibits the Viability of Echinococcus granulosus by Enhancing DNA Damage.
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Authors:
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Gong Y; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Tian C; College of Pharmaceutical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, China.
Lu S; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Gao Y; College of Pharmaceutical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, China.
Wen L; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Chen B; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Gao H; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Zhang H; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Zhao J; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Wang J; First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
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Source:
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DNA and cell biology [DNA Cell Biol] 2021 Jan; Vol. 40 (1), pp. 1-9. Date of Electronic Publication: 2020 Nov 10.
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Publication Type:
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Journal Article
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Language:
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English
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Imprint Name(s):
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Publication: Larchmont, NY : Mary Ann Liebert
Original Publication: [New York, NY] : Mary Ann Liebert, [c1990-
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MeSH Terms:
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DNA Damage*
Echinococcus granulosus/*drug effects
Harmine/*toxicity
Helminth Proteins/*genetics
X-linked Nuclear Protein/*genetics
Animals ; DNA Topoisomerases, Type II/genetics ; DNA Topoisomerases, Type II/metabolism ; Echinococcus granulosus/genetics ; Harmine/analogs & derivatives ; Helminth Proteins/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; X-linked Nuclear Protein/metabolism
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Contributed Indexing:
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Keywords: DNA damage; Echinococcus granulosus; EgRad54
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Substance Nomenclature:
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0 (Helminth Proteins)
0 (Tumor Suppressor Protein p53)
4FHH5G48T7 (Harmine)
EC 3.6.4.12 (X-linked Nuclear Protein)
EC 5.99.1.3 (DNA Topoisomerases, Type II)
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Entry Date(s):
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Date Created: 20201110 Date Completed: 20210202 Latest Revision: 20210202
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Update Code:
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20240105
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DOI:
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10.1089/dna.2020.5779
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PMID:
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33170025
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This study aimed at exploring the role of EgRad54 and the effect of harmine (HM) or HM derivatives (HMDs) on DNA damage in Echinococcus granulosus. DNA damage in E. granulosus protoscoleces (PSCs) was assessed by using a comet assay, after treatment with HM or HMDs. Efficiency of electroporation-based transfection of PSCs and subsequent EgRad54 knockdown was evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR) and fluorescence intensity. Viability of PSCs was determined via eosin exclusion test, and expression of related genes was analyzed via RT-qPCR. HM and HMDs significantly ( p < 0.05) increased DNA damage in E. granulosus, and upregulated EgRad54 expression. Compared with HM and HMD-only treatment groups, EgRad54 knockdown combined with HM and HMD treatment further reduced E. granulosus viability. This combined approach resulted in significant ( p < 0.05) downregulation of Rad54 and Topo2a expression, and upregulation of ATM expression, whereas H2A and P53 expression was significantly higher compared with control groups. These data show that EgRad54 knockdown, combined with HM or HMD treatment, enhances DNA damage in E. granulosus via upregulation of ATM and H2A , and downregulation of Rad54 and Topo2a , thereby inhibiting E. granulosus growth, and suggest that EgRad54 is a potential therapeutic target for cystic echinococcosis treatment.
