Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia

Author:

Rattanaporn Patchara12,Tongsima Sissades34ORCID,Mandrup-Poulsen Thomas5ORCID,Svasti Saovaros26,Tanyong Dalina1

Affiliation:

1. Department of Clinical Microscopic, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand

2. Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand

3. National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani, Thailand

4. National Center for Genetics Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand

5. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

6. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand

Abstract

Background Diabetes mellitus (DM) is a common complication found in β-thalassemia patients. The mechanism of DM in β-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-β (IL-1β) and tumor necrosis factor-α (TNF-α). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1β and TNF-α, on 1.1B4 human pancreatic β-cell line. Methods The effect of the combination of FAC and cytokines on cell viability was studied by MTT assay. Insulin secretion was assessed by the enzyme-linked immunosorbent assay (ELISA). The reactive oxygen species (ROS) and cell apoptosis in normal and high glucose condition were determined by flow cytometer. In addition, gene expression of apoptosis, antioxidant; glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2), and insulin secretory function were studied by real-time polymerase chain reaction (Real-time PCR). Results The findings revealed that FAC exposure resulted in the decrease of cell viability and insulin-release, and the induction of ROS and apoptosis in pancreatic cells. Interestingly, a combination of FAC and cytokines had an additive effect on SOD2 antioxidants’ genes expression and endoplasmic reticulum (ER) stress. In addition, it reduced the insulin secretion genes expression; insulin (INS), glucose kinase (GCK), protein convertase 1 (PSCK1), and protein convertase 2 (PSCK2). Moreover, the highest ROS and the lowest insulin secretion were found in FAC combined with IL-1β and TNF-α in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in β-thalassemia patients.

Funder

Mahidol University Research Grants, Research Chair Grant, NSTDA

National Research University Initiative

Thailand Graduate Institute of Science and Technology (TGIST), NSTDA

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference35 articles.

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2. Cytokines and pancreatic beta-cell apoptosis;Berchtold;Advances in Clinical Chemistry,2016

3. Regulators of iron homeostasis: new players in metabolism, cell death, and disease;Bogdan;Trends in Biochemical Sciences,2016

4. Mechanisms of ferroptosis;Cao;Cellular and Molecular Life Sciences,2016

5. The role of iron and reactive oxygen species in cell death;Dixon;Nature Chemical Biology,2014

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