Plumbagin induces RPE cell cycle arrest and apoptosis via p38 MARK and PI3K/AKT/mTOR signaling pathways in PVR

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Abstract

Background

This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism.

Methods

Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 μM) of PLB for 24 h or with 15 μM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR.

Results

PLB exhibited potent inducing effects on cell cycle arrest at G2/M phase and apoptosis of ARPE cells via the modulation of Bcl-2 family regulators in a concentration- and time-dependent manner. PLB induced inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways contributing to the anti-proliferative activities in ARPE cells.

Conclusions

This is the first report to show that PLB could inhibit the proliferation of RPE cells through down-regulation of modulatory signaling pathways. The results open new avenues for the use of PLB in prevention and treatment of proliferative vitreoretinopathy.

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Most cited references 26

Record: found
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Mitochondrial regulation of cell cycle and proliferation.

Valeria Antico Arciuch, María Eugenia Elguero, Juan Poderoso … (2012)

Eukaryotic mitochondria resulted from symbiotic incorporation of α-proteobacteria into ancient archaea species. During evolution, mitochondria lost most of the prokaryotic bacterial genes and only conserved a small fraction including those encoding 13 proteins of the respiratory chain. In this process, many functions were transferred to the host cells, but mitochondria gained a central role in the regulation of cell proliferation and apoptosis, and in the modulation of metabolism; accordingly, defective organelles contribute to cell transformation and cancer, diabetes, and neurodegenerative diseases. Most cell and transcriptional effects of mitochondria depend on the modulation of respiratory rate and on the production of hydrogen peroxide released into the cytosol. The mitochondrial oxidative rate has to remain depressed for cell proliferation; even in the presence of O₂, energy is preferentially obtained from increased glycolysis (Warburg effect). In response to stress signals, traffic of pro- and antiapoptotic mitochondrial proteins in the intermembrane space (B-cell lymphoma-extra large, Bcl-2-associated death promoter, Bcl-2 associated X-protein and cytochrome c) is modulated by the redox condition determined by mitochondrial O₂ utilization and mitochondrial nitric oxide metabolism. In this article, we highlight the traffic of the different canonical signaling pathways to mitochondria and the contributions of organelles to redox regulation of kinases. Finally, we analyze the dynamics of the mitochondrial population in cell cycle and apoptosis.

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Record: found
Abstract: found
Article: not found

Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis.

Feifan Zhou, Ying Yang, Da Xing (2011)

Autophagy and apoptosis play important roles in the development, cellular homeostasis and, especially, oncogenesis of mammals. They may be triggered by common upstream signals, resulting in combined autophagy and apoptosis. In other instances, they may be mutually exclusive. Recent studies have suggested possible molecular mechanisms for crosstalk between autophagy and apoptosis. Bcl-2 and Bcl-xL, the well-characterized apoptosis guards, appear to be important factors in autophagy, inhibiting Beclin 1-mediated autophagy by binding to Beclin 1. In addition, Beclin 1, Bcl-2 and Bcl-xL can cooperate with Atg5 or Ca(2+) to regulate both autophagy and apoptosis. Thus, Bcl-2 and Bcl-xL represent a molecular link between autophagy and apoptosis. Here, we discuss the possible roles of Bcl-2 and Bcl-xL in apoptosis and autophagy, and the crosstalk between them. © 2010 The Authors Journal compilation © 2010 FEBS.

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Record: found
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Article: not found

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences.

J Pastor, Jimena Rojas, Salvador Pastor-Idoate … (2016)

During the last four decades, proliferative vitreoretinopathy (PVR) has defied the efforts of many researchers to prevent its occurrence or development. Thus, PVR is still the major complication following retinal detachment (RD) surgery and a bottle-neck for advances in cell therapy that require intraocular surgery. In this review we tried to combine basic and clinical knowledge, as an example of translational research, providing new and practical information for clinicians. PVR was defined as the proliferation of cells after RD. This idea was used for classifying PVR and also for designing experimental models used for testing many drugs, none of which were successful in humans. We summarize current information regarding the pathogenic events that follow any RD because this information may be the key for understanding and treating the earliest stages of PVR. A major focus is made on the intraretinal changes derived mainly from retinal glial cell reactivity. These responses can lead to intraretinal PVR, an entity that has not been clearly recognized. Inflammation is one of the major components of PVR, and we describe new genetic biomarkers that have the potential to predict its development. New treatment approaches are analyzed, especially those directed towards neuroprotection, which can also be useful for preventing visual loss after any RD. We also summarize the results of different surgical techniques and clinical information that is oriented toward the identification of high risk patients. Finally, we provide some recommendations for future classification of PVR and for designing comparable protocols for testing new drugs or techniques.

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Author and article information

Contributors

Haiting Chen: c0bg0he@126.com

Huifang Wang: gfahoag@126.com

Jianbin An: jianbinan2011@163.com

Qingli Shang: qinglishang2015@163.com

Jingxue Ma: 0086-15803210925 , majingxue2000@163.com

Journal

Journal ID (nlm-ta): BMC Complement Altern Med

Journal ID (iso-abbrev): BMC Complement Altern Med

Title: BMC Complementary and Alternative Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6882

Publication date (Electronic): 13 March 2018

Publication date PMC-release: 13 March 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 89

Affiliations

[1 ]ISNI 0000 0004 1804 3009, GRID grid.452702.6, Department of Ophthalmology, , Second Hospital of Hebei Medical University, ; No. 215 Peace West Road, Qiaoxi District, Shijiazhuang, Hebei 050000 China

[2 ]ISNI 0000 0004 0614 4777, GRID grid.452270.6, Department of Ophthalmology, , Cangzhou Central Hospital, ; No. 16 Xinhua West Road, Cangzhou, Hebei 061000 China

Article

Publisher ID: 2155

DOI: 10.1186/s12906-018-2155-3

PMC ID: 5851073

PubMed ID: 29534723

SO-VID: 78c84d91-8d6d-4385-95cf-1fa09a84e3d9

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.