scholarly journals Melatonin Suppresses Iron-Induced Apoptosis by Activating the Nrf2/HO-1 Signaling Pathway in Osteoblast

2021 ◽  
Author(s):  
Hongdong Ma ◽  
Zhiqing Li ◽  
Jiao Chu ◽  
Dali Yin
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Oxygen Species ◽  
Apoptosis Rate ◽  
Excess Iron ◽  
Associated Proteins ◽  
Ferric Ammonium ◽  
Induced Apoptosis

Abstract Objective To investigate the effect of melatonin on the apoptosis of hFOB1.19 cells induced by excess iron. Methods The hFOB1.19 cells were treated with ferric ammonium citrate (300 μmol/L) and melatonin (100 μmol/L) for 24 h. The apoptosis rate and the level of reactive oxygen species (ROS) were analyzed using flow cytometry. Expression of proteins associated with apoptosis, such as Bax and caspase-3, and those associated with the Nrf-2 signaling pathway such as Nrf2 and HO-1 were analyzed using western blotting. Results The level of ROS and the apoptosis rate increased after intervention with excess iron. The levels of Bax in the mitochondria and cleaved caspase-3 in the cytosol increased. However, after pretreatment with melatonin, the level of ROS, apoptosis rate, and expression of apoptosis-associated proteins decreased, and the expression of Nrf2 and HO-1 increased. Conclusion Melatonin inhibits the level of oxidation in osteoblasts via the Nrf2/HO-1 signal pathway, resulting in the reduction of apoptosis induced by excess iron.

Iron overload induced by ferric ammonium citrate triggers reactive oxygen species-mediated apoptosis via both extrinsic and intrinsic pathways in human hepatic cells

2015 ◽  
Vol 35 (6) ◽  
pp. 598-607 ◽  
Author(s):  
S-W Li ◽  
C-M Liu ◽  
J Guo ◽  
AM Marcondes ◽  
J Deeg ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ferric Ammonium

Background: Hepatic iron overload is common in patients with myelodysplastic syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better understand the mechanisms of iron overload-induced liver injury, we examined the effects of iron overload induced by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling pathway in human hepatic cell line HH4. Methods and Results: Hepatic HH4 cells were exposed to FAC to force iron uptake, and cellular responses were determined. Incubation with 5 mM FAC resulted in increased intracellular iron content in a time-dependent manner. High concentration of FAC impaired cell viability and increased level of reactive oxygen species (ROS), and addition of antioxidant reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced intracellular ROS generation. FAC overload significantly increased the phosphorylation of inhibitor of κB-α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor κ light chain enhancer of activated B cells (NF-κB) p65 and promoted the nuclear translocation of NF-κB p65. Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4 cells resulted in restoration of cell viability. Conclusions: We reported that FAC treatment is capable of inducing both extrinsic death receptor and intrinsic mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS-activated p38 MAPK and NF-κB pathways.

scholarly journals Zearalenone Induces Endothelial Cell Apoptosis through Activation of a Cytosolic Ca2+/ERK1/2/p53/Caspase 3 Signaling Pathway

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 187
Author(s):  
Hyeon-Ju Lee ◽  
Se-Young Oh ◽  
Inho Jo
Keyword(s):  
Signaling Pathway ◽  
Small Interfering Rna ◽  
Caspase 3 ◽  
Cytosolic Calcium ◽  
Receptor Activation ◽  
Oxygen Species ◽  
Endothelial Cell Apoptosis ◽  
Induced Apoptosis ◽  
Interfering Rna ◽  
Specific Inhibitors

Zearalenone (ZEN) is a mycotoxin that has been reported to damage various types of cells/tissues, yet its effects on endothelial cells (ECs) have never been investigated. Therefore, this study investigates the potential effects of ZEN using bovine aortic ECs (BAECs). In this study, we found that ZEN induced apoptosis of BAECs through increased cleavage of caspase 3 and poly ADP-ribose polymerase (PARP). ZEN also increased phosphorylation of ERK1/2 and p53, and treatment with the ERK1/2 or p53 inhibitor reversed ZEN-induced EC apoptosis. Transfection of BAECs with small interfering RNA against ERK1/2 or p53 revealed ERK1/2 as an upstream target of p53 in ZEN-stimulated apoptosis. ZEN increased the production of reactive oxygen species (ROS), yet treatment with the antioxidant did not prevent EC apoptosis. Similarly, blocking of estrogen receptors by specific inhibitors also did not prevent ZEN-induced apoptosis. Finally, chelation of cytosolic calcium (Ca2+) using BAPTA-AM or inhibition of endoplasmic reticulum (ER) Ca2+ channel using 2-APB reversed ZEN-induced EC apoptosis, but not by inhibiting ER stress using 4-PBA. Together, our findings demonstrate that ZEN induces EC apoptosis through an ERK1/2/p53/caspase 3 signaling pathway activated by Ca2+ release from the ER, and this pathway is independent of ROS production and estrogen receptor activation.

scholarly journals β-Elemene Triggers ROS-dependent Apoptosis in Glioblastoma Cells Through Suppressing STAT3 Signaling Pathway

2021 ◽  
Vol 27 ◽  
Author(s):  
Shi-zhong Cai ◽  
Qian-wei Xiong ◽  
Li-na Zhao ◽  
Yi-ting Ji ◽  
Zheng-xiang Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Treatment Strategies ◽  
Oxygen Species ◽  
Glioblastoma Cells ◽  
Western Blot Assay ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Apoptotic Activity ◽  
Induced Apoptosis

Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. β-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in β-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that β-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with β-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that β-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of p-JAK2 and p-Src. Moreover, pre-incubation of cells with ROS inhibitor N-acetyl-L-cysteine (NAC) significantly reversed β-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of β-elemene in glioblastoma cells.

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

scholarly journals A study on the aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous fumarate, ferrous sulphate and ferric ammonium citrate, among the rural anaemic women, in the Indian spectrum

2019 ◽  
Vol 8 (12) ◽  
pp. 2751
Author(s):  
Moumita Hazra
Keyword(s):  
Ferrous Sulphate ◽  
Haemoglobin Concentration ◽  
Significant Rise ◽  
Demographic Characteristics ◽  
Health Concern ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ferrous Fumarate ◽  
Ferrous Ascorbate ◽  
Ferric Ammonium

Background: Anaemia is a global health concern, associated with increased maternal and perinatal mortality, preterm delivery, low birth weight, extreme fatigue and impaired immune system; and controlled by oral haematinics; with a rise in haemoglobin concentration. The objective was to examine the various aspects of pharmacoepidemiology and pharmacohaemovigilance of oral haematinics, among the anaemic women population, in rural India.Methods: This was a multi-centre, retrospective, observational and analytical study of the hospital medical records of 250 anaemic patients, who were allocated into group A of 125 patients within 15-21 years and group B of 125 patients within 22-35 years. The patients were prescribed oral haematinics, containing 60 mg of elemental iron, thrice daily, with meals. The various aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous sulphate, ferrous fumarate and ferric ammonium citrate, including patients’ demographic characteristics, anaemic symptoms assessment, prescription patterns, and safety assessment, on 1st, 2nd, 3rd months and follow-up visits, were recorded and thoroughly analysed..Results: In groups A and B, the demographic characteristics of the patients were comparable; ferrous ascorbate was the most commonly prescribed oral haematinic, followed by ferrous sulphate, ferrous fumarate and ferric ammonium citrate, which controlled mild to moderate iron deficiency anaemia, with a gradual significant rise in haemoglobin concentration, in the successive 3 months; and adverse effects were observed to be statistically non-significant in either group.Conclusions: The different aspects of pharmacoepidemiology and pharmacohaemovigilance in the study established that the oral haematinics were reasonably beneficial and safe among the anaemic women population, in rural India.

THE EFFECT OF CERTAIN ORAL AND INJECTABLE IRON PREPARATIONS ON THE BLOOD OF BABY PIGS

1959 ◽  
Vol 39 (2) ◽  
pp. 193-201 ◽  
Author(s):  
H. Doornenbal
Keyword(s):  
Oral Iron ◽  
Ammonium Citrate ◽  
Normal Blood ◽  
Ferric Ammonium Citrate ◽  
Iron Dextran ◽  
Ferric Ammonium ◽  
Iron Sulphate

Haemoglobin levels, haematocrit values and erythrocyte counts were determined at weekly intervals from 3 to 45 days of age for 60 pigs which received iron in the form of: injectable iron-dextran (A); injectable iron-dextran (B); injectable ferric ammonium citrate; oral iron in the form of paste, or sods sprinkled with iron sulphate. The iron-dextran and ferric ammonium citrate compounds were administered at 3 days of age as single injections supplying 100 mgm. of iron and 30 mgm. of ferric ammonium citrate respectively. The paste was administered at 3, 10, 17 and 24 days of age. Sods were fed twice a week during the period of 3 days to 28 days of age.The sod treatment maintained normal blood values while the iron-dextran compounds and the paste resulted in values somewhat below normal, although visible evidence of anaemia was not apparent. Blood values for the group receiving ferric ammonium citrate were extremely low and two pigs on this treatment died at 42 and 60 days of age. Both exhibited severe anaemia.Significant differences were obtained in weaning weights. The heaviest pigs were those receiving sods; the lightest pigs those receiving injectable ferric ammonium citrate. The effect of the different treatments on growth was not apparent until after 21 days of age.

scholarly journals UFL1 Alleviates LPS-Induced Apoptosis by Regulating the NF-κB Signaling Pathway in Bovine Ovarian Granulosa Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 260 ◽  
Author(s):  
Xinling Wang ◽  
Chengmin Li ◽  
Yiru Wang ◽  
Lian Li ◽  
Zhaoyu Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Protein Concentration ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Ovarian Granulosa Cells ◽  
Induced Apoptosis ◽  
Apoptosis Level ◽  
Lps Treatment

Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an E3 ligase of ubiquitin fold modifier 1 (UFM1), which can act together with its target protein to inhibit the apoptosis of cells. Lipopolysaccharides (LPS) can affect the ovarian health of female animals by affecting the apoptosis of ovarian granulosa cells. The physiological function of UFL1 on the apoptosis of bovine (ovarian) granulosa cells (bGCs) remains unclear; therefore, we focused on the modulating effect of UFL1 on the regulation of LPS-induced apoptosis in ovarian granulosa cells. Our study found that UFL1 was expressed in both the nucleus and cytoplasm of bGCs. The results here demonstrated that LPS caused a significant increase in the apoptosis level of bGCs in cows, and also dramatically increased the expression of UFL1. Furthermore, we found that UFL1 depletion caused a significant increase in apoptosis (increased the expression of BAX/BCL-2 and the activity of caspase-3). Conversely, the overexpression of UFL1 relieved the LPS-induced apoptosis. In order to assess whether the inhibition of bGCs apoptosis involved in the nuclear factor-κB (NF-κB) signaling pathway resulted from UFL1, we detected the expression of NF-κB p-p65. LPS treatment resulted in a significant upregulation in the protein concentration of NF-κB p-p65, and knockdown of UFL1 further increased the phosphorylation of NF-κB p65, while UFL1 overexpression significantly inhibited the expression of NF-κB p-p65. Collectively, UFL1 could suppress LPS-induced apoptosis in cow ovarian granulosa cells, likely via the NF-κB pathway. These results identify a novel role of UFL1 in the modulation of bGC apoptosis, which may be a potential signaling target to improve the reproductive health of dairy cows.

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