Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray

Motoko Nakayama; Etsuko Ueta; Mitsuru Yoshida; Yuri Shimizu; Atsuko Tokuda; Yasuko Sone; Yuri Nomi; Y Otsuka

doi:10.1080/13510002.2023.2247150

Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray

Redox Rep. 2023 Dec;28(1):2247150. doi: 10.1080/13510002.2023.2247150.

Authors

Motoko Nakayama¹, Etsuko Ueta², Mitsuru Yoshida¹, Yuri Shimizu^{1

3}, Atsuko Tokuda¹, Yasuko Sone^{1

4}, Yuri Nomi^{1

5}, Y Otsuka¹

Affiliations

¹ Department of Life Science, Graduate School, Ochanomizu University, Tokyo, Japan.
² School of Health Science, Faculty of Medicine, Tottori University, Tottori, Japan.
³ Department of Food Business, Nihon University, Kanagawa, Japan.
⁴ Department of Health and Nutrition, Takasaki University of Health and Welfare, Gunma, Japan.
⁵ Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.

Abstract

Pancreatic islet β-cells weaken under oxidative stress. In this study, human pancreatic islet-derived 1.1B4 cells were exposed to H₂O₂ and analysed using a human microarray, which revealed that heme oxygenase 1 (HMOX1), glutamate-cysteine ligase, early growth response 1, nuclear receptor subfamily 4 group A member 3 (NR4A3) and jun B proto-oncogene were upregulated, whereas superoxide dismutase 1 and catalase were not. Expression of NR4A3 rapidly increased after H₂O₂ addition, and the 1.1B4 cells treated with siRNA targeting NR4A3 became sensitive to H₂O₂; further, HMOX1 expression was strongly inhibited, suggesting that NR4A3 is an oxidative stress-responsive transcription factor that functions through HMOX1 expression in pancreatic islet β-cells. Expression of cyclin E1 and cyclin-dependent kinase 1 was also inhibited by siRNAs targeting NR4A3.

Keywords: CDK2; HMOX1; NR4A3; Pancreatic β-cells; microarray; oxidative stress; siNR4A3; transcription factor.

MeSH terms

Antioxidants / metabolism
DNA-Binding Proteins / metabolism
Humans
Hydrogen Peroxide / pharmacology
Islets of Langerhans* / metabolism
Oxidative Stress
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptors, Steroid* / metabolism
Receptors, Thyroid Hormone / metabolism

Substances

Antioxidants
DNA-Binding Proteins
Hydrogen Peroxide
NR4A3 protein, human
Receptors, Steroid
Receptors, Thyroid Hormone
RNA, Small Interfering

Grants and funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (A, B, and C)] under Grant numbers 17500533, 20300243, 24240096, and 25282020; and Grant-in-Aid for Challenging Exploratory Research under Grant number 21650196.