The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid β Induced Production of Angiogenic Factors b y ARPE-19 Cells

Wu, Longxi; Tan, Xiaoyu; Liang, Luodan; Yu, Hongsong; Wang, C.; Zhang, D.; Kijlstra, Aize; Yang, Peizeng

doi:10.2174/1566524017666170331162616

Cited by 21 publications

(17 citation statements)

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“…This process leads to iC3b deposition and subsequent clearance of the internalized apoptotic debris. Increased C3 (and C5) activation in ARPE-19 cells upon treatment with amiloyd-β was also observed in another study and is associated with increased mitochondrial ROS production (Wu et al, 2017). C1q was also shown to unexpectedly play role in the eye during the development of age-related macular degeneration (AMD) (Doyle et al, 2012) by binding to drusen deposits and supporting the NLRP3 inflammasome activation in monocytes which resulted in secretion of proinflammatory IL-1β.…”

Section: The Complosome In Non-immune Cellsmentioning

confidence: 67%

Intracellular complement − the complosome − in immune cell regulation

Arbore

Kemper

Kolev

2017

Molecular Immunology

166

158

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The complement system was defined over a century ago based on its ability to "complement" the antibody-mediated and cell-mediated immune responses against pathogens. Today our understanding of this ancient part of innate immunity has changed substantially and we know now that complement plays an undisputed pivotal role in the regulation of both innate and adaptive immunity. The complement system consists of over 50 blood-circulating, cell-surface expressed and intracellular proteins. It is key in the recognition and elimination of invading pathogens, also in the removal of self-derived danger such as apoptotic cells, and it supports innate immune responses and the initiation of the general inflammatory reactions. The long prevailing classic view of complement was that of a serum-operative danger sensor and first line of defence system, however, recent experimental and clinical evidences have demonstrated that "local" tissue and surprisingly intracellular complement (the complosome) activation impacts on normal cell physiology. This review will focus on novel aspects of intracellular complement activation and its unexpected roles in basic cell processes such as metabolism. We also discuss what the existence of the complosome potentially means for how the host handles intracellular pathogens such as viruses.

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Section: The Complosome In Non-immune Cellsmentioning

confidence: 67%

Intracellular complement − the complosome − in immune cell regulation

Arbore

Kemper

Kolev

2017

Molecular Immunology

166

158

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“…Previous studies reported (Albrecht et al, 2004;Laudes et al, 2002) that ECs can synthesize complement component C3, that the complement activation fragment C5a can affect EC responses in vitro, and that the generation of C3a and/or C5a activation fragments accompanies numerous disease states (Alawieh et al, 2015;Lillegard et al, 2014;Facciabene et al, 2017;Lechner et al, 2016;Wu et al, 2017). These findings uniformly were interpreted in the context of systemic complement activation.…”

Section: Introductionmentioning

confidence: 91%

VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R–gp130

Hwang

Strainic

Pohlmann

et al. 2019

Journal of Cell Science

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Purified vascular endothelial cell (EC) growth factor receptor-2 (VEGFR2) auto-phosphorylates upon VEGF-A occupation in vitro, arguing that VEGR2 confers its mitotic and viability signaling in and of itself. Herein, we show that, in ECs, VEGFR2 function requires concurrent C3a/C5a receptor (C3ar1/C5ar1) and IL-6 receptor (IL-6R)-gp130 co-signaling. C3ar1/C5ar1 or IL-6R blockade totally abolished VEGFR2 auto-phosphorylation, downstream Src, ERK, AKT, mTOR and STAT3 activation, and EC cell cycle entry.

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“…The percentage of 8-OHdG-positive nuclei was significantly higher in the Aβ 1-40 -treated cells after 12 h and 24 h than in the untreated cells (Figure 4 B). Previous studies have shown that the mitochondria and the NADPH oxidase system are the two major sources of ROS overproduction induced by Aβ 1-40 33 - 35 .…”

Section: Resultsmentioning

confidence: 99%

“…NOX4 and mtROS also exhibit a clear link with inflammation. Mitochondrial NOX4 was reported to promote NLRP3 inflammasome activation through the fatty acid oxidation (FAO) pathway 57 , and mtROS was shown to regulate Aβ-induced proinflammatory cytokine expression 35 . Inflammatory cytokine production affected TLR5-NOX4-ROS signaling-mediated NF-κB activation 18 , which was demonstrated to be a critical regulator in RPE-mediated inflammation, as reported in our previous study 7 .…”

Section: Discussionmentioning

confidence: 99%

ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22^phox activation in Aβ-induced retinal pigment epithelial cell injury

Sun¹,

Chen²,

Li³

et al. 2020

Theranostics

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Rationale: Amyloid β (Aβ) deposition, an essential pathological process in age-related macular degeneration (AMD), causes retinal pigment epithelium (RPE) degeneration driven mostly by oxidative stress. However, despite intense investigations, the extent to which overoxidation contributes to Aβ-mediated RPE damage and its potential mechanism has not been fully elucidated. Methods: We performed tandem mass-tagged (TMT) mass spectrometry (MS) and bioinformatic analysis of the RPE-choroid complex in an Aβ 1-40 -induced mouse model of retinal degeneration to obtain a comprehensive proteomic profile. Key regulators in this model were confirmed by reactive oxygen species (ROS) detection, mitochondrial ROS assay, oxygen consumption rate (OCR) measurement, gene knockout experiment, chromatin immunoprecipitation (ChIP), and luciferase assay. Results: A total of 4243 proteins were identified, 1069 of which were significantly affected by Aβ 1-40 and found to be enriched in oxidation-related pathways by bioinformatic analysis. Moreover, NADPH oxidases were identified as hub proteins in Aβ 1-40 -mediated oxidative stress, as evidenced by mitochondrial dysfunction and reactive oxygen species overproduction. By motif and binding site analyses, we found that the transcription factor PU.1/Spi1 acted as a master regulator of the activation of NADPH oxidases, especially the NOX4-p22 phox complex. Also, PU.1 silencing impeded RPE oxidative stress and mitochondrial dysfunction and rescued the retinal structure and function. Conclusion: Our study suggests that PU.1 is a novel therapeutic target for AMD, and the regulation of PU.1 expression represents a potentially novel approach against excessive oxidative stress in Aβ-driven RPE injury.

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The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid β Induced Production of Angiogenic Factors b y ARPE-19 Cells

Cited by 21 publications

References 0 publications

Intracellular complement − the complosome − in immune cell regulation

Intracellular complement − the complosome − in immune cell regulation

VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R–gp130

ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22^phox activation in Aβ-induced retinal pigment epithelial cell injury

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The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid β Induced Production of Angiogenic Factors b y ARPE-19 Cells

Cited by 21 publications

References 0 publications

Intracellular complement − the complosome − in immune cell regulation

Intracellular complement − the complosome − in immune cell regulation

VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R–gp130

ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22phox activation in Aβ-induced retinal pigment epithelial cell injury

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ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22^phox activation in Aβ-induced retinal pigment epithelial cell injury