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

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Pancreatic β-cells
• oxidative stress
• microarray
• HMOX1
• NR4A3
• siNR4A3
• transcription factor
• CDK2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Disclosure of interest

The authors report there are no competing interests to declare.

Data availability statement

The datasets are available from the corresponding author upon reasonable request.

Preprints

https://www.biorxiv.org/content/10.1101/2021.08.20.457070v1

Additional information

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.