Iron overload induces apoptosis of murine preosteoblast cells via <scp>ROS</scp> and inhibition of <scp>AKT</scp> pathway

Ke, Jun‐Yu; Cen, Wan‐Jing; Zhou, Xin; Li, Ye‐Rong; Kong, Weidong; Jiang, Jianwei

doi:10.1111/odi.12662

Cited by 32 publications

(23 citation statements)

References 38 publications

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“…Firstly, we found that iron exposure resulted in a reduction of cell viability, induction of ROS, and increasing of apoptosis in a dose-dependent manner in 1.1B4 cells that have been previously reported in other types of cell line such as HH4, human hematopoietic cells/mesenchymal cells, MC3T3-E1 cells, and MG-63 cells through different mechanisms (Li et al, 2016;Lu et al, 2013;Doyard et al, 2012;Yang et al, 2017;Ke et al, 2017). Many reports have been demonstrated that iron overload lead to increasing intracellular ROS and caused cell damage, which is concomitant with our results.…”

Section: Discussionsupporting

confidence: 66%

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

Rattanaporn

Tongsima

Mandrup‐Poulsen

et al. 2020

PeerJ

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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.

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Section: Discussionsupporting

confidence: 66%

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

Rattanaporn

Tongsima

Mandrup‐Poulsen

et al. 2020

PeerJ

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“…Caspase-3 is widely recognized as a pro-apoptosis factor [22]. Meanwhile, AKT signaling pathway is closely associated with cell growth [23,24]. In the current study, we found the protein content of cleaved caspase-3 was upregulated in miR-338-5p mimic transfected cells.…”

Section: Mir-338-5p Overexpression Suppressed the Growth And Invasionsupporting

confidence: 49%

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Wen

Chen

et al. 2020

Reprod. Sci.

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Selective intrauterine growth restriction (sIUGR) is a disorder of monochorionic (MC) twin pregnancies. However, the underlying mechanism remains largely unknown. Trophoblast cells are the major component of the placenta. Dysfunction of trophoblast cells is associated with placental dysfunction. Our previous study identified miR-338-5p is downregulated in placenta tissues sharing larger twins of sIUGR. In the present study, we aimed to investigate the role of miR-338-5p in trophoblast cells and explored its target. Our results further indicated that miR-338-5p was downregulated in placental tissues supporting larger twins of sIUGR, whereas epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was upregulated. Moreover, miR-338-5p overexpression suppressed the growth and invasion of trophoblast cells. Importantly, results from luciferase reporter assay demonstrated that miR-338-5p bound on the 3′-UTR of EFEMP1. miR-338-5p suppressed the growth and invasion of trophoblast cells via targeting EFEMP1. Further, miR-338-5p/EFEMP1 might disrupt the function of trophoblast cells via inhibiting the phosphorylation of AKT.

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“…Studies in vitro and in vivo have indicated that iron overload induces differentiation of osteoclasts and inhibits proliferation of osteoblasts by catalyzing the generation of ROS (He et al, ; Lu et al, ). In addition, our previous study shows that iron overload induces apoptosis of murine preosteoblast cells via ROS and inhibition of the AKT pathway (Ke et al, ). Periodontal disease patients experience a periodontal iron overload state, which may inhibit the growth of osteoblasts in the alveolar bone.…”

Section: Discussionmentioning

confidence: 96%

Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells

Cen¹,

Feng²,

Li³

et al. 2018

Journal Cellular Physiology

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This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload in MC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3, and their downstream proteins were detected with Western blot assays. The results showed that the iron levels of MC3T3-E1 cells increased with increasing concentrations of FAC. High levels of ferric ion inhibited proliferation of MC3T3-E1 cells and increased their ROS levels. Additionally, iron overload induced G1arrest in MC3T3-E1 cells and down-regulated the expression of Cyclin D , Cyclin D , CDK2, CDK4 and CDK6, but up-regulated p27 Kip1. In addition, the expression levels of Beclin-1 and LC3 II increased, but that of p62 decreased. Further experiments showed that the phosphorylation of AKT and its downstream proteins p-GSK-3β(Ser9) and p-mTOR (Ser2448) were decreased. The levels of p-p38 and p53 were up-regulated while those of cdc25A and p-ERK 1/2 were down-regulated. Phosphorylation of Stat3 and its downstream proteins was all decreased. These results show that iron overload generates ROS, blocks the PI3K/AKT and Jak/Stat3 signal pathways, and activates p38 MAPK, subsequently inducing G1 arrest and autophagy in MC3T3-E1 cells.

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Iron overload induces apoptosis of murine preosteoblast cells via ROS and inhibition of AKT pathway

Abstract: Iron overload can generate ROS in cells, inhibit AKT kinase and its downstream proteins activity, and subsequently initiate apoptotic events.

Cited by 32 publications

References 38 publications

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

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

miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells

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