In VitroAnalysis of Mitochondrial Unfolded Protein Response and Expression of HSPA9, HSPD1 and ATF5 using Cell Culture Models

Received: 17-04-2023

Accepted: 20-11-2023

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Issue: Vol. 21 No. 11 (2023)

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CHĂN NUÔI – THÚ Y – THỦY SẢN

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Nguyen, T., Kambe, Y., Giap, N., Ngan, M., Tra, V., Le, H., & Dao, B. (2024). In VitroAnalysis of Mitochondrial Unfolded Protein Response and Expression of HSPA9, HSPD1 and ATF5 using Cell Culture Models. Vietnam Journal of Agricultural Sciences, 21(11), 1404–1412. http://testtapchi.vnua.edu.vn/index.php/vjasvn/article/view/1209

In VitroAnalysis of Mitochondrial Unfolded Protein Response and Expression of HSPA9, HSPD1 and ATF5 using Cell Culture Models

Thanh Trung Nguyen (*) 1, 2 , Yuki Kambe 3 , Nguyen Van Giap 1 , Mai Thi Ngan 1 , Vu Thi Thu Tra 1 , Huynh Thi My Le 1 , Bui Tran Anh Dao 1

  • 1 Khoa Thú y, Học viện Nông nghiệp Việt Nam
  • 2 Department of Pharmacology, Toxicology, Internal Medicine and Diagnostics, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi, Vietnam
  • 3 Trường Đại học Kagoshima, Nhật Bản

    • Keywords

    CDDO, in vitro, Paraquat, UPRmtand mitochondrial stress

    Abstract


    This study aimed to assess the role of the mitochondrial chaperones signaling factors induced by the mammalian mitochondrial unfolded protein response. In vitromodels were used with the mRNA of Hspa9, Hspd1 and ATF5 gene measured upon mitochondrial stress via Paraquat and 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid in NIH3T3 and HEK293 cell lines by quantitative real time Polymerase Chain Reaction. The results demonstrated that NIH3T3 cells were not suitable as a readout for UPRmt induction in vitro. Further, it was found that the levels of the transcription factor ATF5 tended to be decreased, while the upregulation of the Hspa9 and Hspd1 was observed upon mitochondrial stress in the context of the cells treated with 50 or 500μMParaquat or 3μM2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid. Notably, glucose concentration directly affected mammalian mitochondrial unfolded protein response signaling in vitro. Taken together, the results of the study indicates that the HEK293 cell line should be used to evaluate the expression levels of the genes upon mitochondrial stress conditions and might pave the way for the development of novel therapies for the cure of mitochondrial disorders and associated diseases in the future..

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