RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression

Rezatabar, Setareh; Karimian, Ansar; Rameshknia, Vahid; Parsian, Hadi; Majidinia, Maryam; Kopi, Tayebeh Azramezani; Bishayee, Anupam; Sadeghinia, Ali; Yousefi, Mehdi; Monirialamdari, Mohsen; Yousefi, Bahman

doi:10.1002/jcp.28334

Cited by 191 publications

(103 citation statements)

References 99 publications

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“…Mitogen-activated protein kinase (MAPK) pathways regulate a large range of cellular activities, such as gene expression, cell growth, metabolism, survival, apoptosis, and differentiation [29]. In this present study, phosphorylated ERK and p38 proteins were enhanced in histamine-treated neutrophils (Fig.…”

Section: Histamine Enhanced the Phosphorylation Of Erk And P38 Proteinssupporting

confidence: 55%

Characterization of Bovine Neutrophil Extracellular Traps Induced by Histamine

Zhou¹,

Z²,

Zhu³

et al. 2020

Preprint

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BackgroundHistamine plays an central role in many allergic diseases including allergic asthma and allergic rhinitis, and is also involved in bovine laminitis through regulating immune responses. Neutrophil extracellular traps (NETs) formation is a novel effector mechanism of neutrophils to defend against various stimuli. In the present study, we aimed to investigate the role of histamine on bovine NET formation and examined its fundamental molecular mechanisms. ResultsFirstly, the effects of histamine on neutrophil viability was measured by Cell Counting Kit-8 (CCK-8) and Lactate dehydrogenase (LDH) assays. The results showed that histamine had no significant influence on neutrophil viability. Then we characterized histamine-triggered NET formation by confocal microscopy and PicoGreen-derived NETs quantification. Confocal microscopy analyses illustrated NET structures by co-localizing the main components of NETs, and NET quantification revealed that histamine-triggered NETs were released in a dose-dependent manner. In addition, we found reactive oxygen species (ROS) production, phosphorylated extracellular signal-regulated kinase (ERK) and p38 proteins were significantly elevated in histamine-challenged neutrophils. By applying functional inhibitors of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), ERK and p38, histamine-triggered NETs were markedly reduced, indicating their importance in histamine-triggered NET formation. ConclusionsOur findings described histamine-triggered NET formation, and revealed its potential molecular mechanisms via NADPH oxidase, ERK and p38 pathways. This is the first study to depict NET formation induced by histamine, which could provide a new insight into histamine-related diseases.

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Section: Histamine Enhanced the Phosphorylation Of Erk And P38 Proteinssupporting

confidence: 55%

Characterization of Bovine Neutrophil Extracellular Traps Induced by Histamine

Zhou¹,

Z²,

Zhu³

et al. 2020

Preprint

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“…Furthermore, TMEM147 activated the MAPK pathway, as shown by western blotting and verified by IHC in HCC tissues. The MAPK signaling pathway is closely related to tumor progression, and its transcriptional regulation of the cell cycle mediates proliferation, and activation of matrix metalloproteinases to promote invasion and metastasis [28,29]. We confirmed that TMEM147 could bind to EGFR and regulate the downstream MAPK pathway, and further investigated if TMEM147 could affect the growth, metastasis, and glycolysis of HCC cells through EGFR.…”

Section: Discussionmentioning

confidence: 63%

TMEM147 promotes hepatocellular carcinoma progress by inducing EGFR/MAPK activity

Sun¹,

Xu²,

Tian³

et al. 2020

Preprint

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Backgroud: Hepatocellular carcinoma (HCC) is characterized by rapid early proliferation and distant metastasis and is extremely difficult to treat. Aerobic glycolysis is a hallmark of abnormal glucose metabolism in cancer cells as has been shown to be associated with tumor proliferation and metastasis; however, the mechanisms underlying aerobic glycolysis remain unclear.Methods: Immunohistochemistry (IHC) and qRT-PCR was performed to investigate the association between TMEM147 expression and the clinicopathological characteristics and prognosis of patients with HCC. Loss-and gain-of function assays were performed to investigate the role of TMEM147 in proliferation, metastasis and glycolysis in vitro and vivo. Bioinformatic analysis and rescue assay were used to demonstrated the TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane.Results: we identified TMEM147 as a protein that was highly expressed and associated with poor survival in patients with HCC. Both gain-and loss-of-function studies revealed that TMEM147 acted as a key oncoprotein by promoting HCC growth, metastasis, and glycolysis via the EGFR/ MAPK signaling pathway. Mechanistically, TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane, thus increasing the stability of EGFR and prolonging activation of the downstream MAPK pathway. Conclusion:Collectively, these results demonstrated the role and functional mechanism of TMEM147 in HCC, and indicated that TMEM147 may represent a prognostic biomarker and potential therapeutic target for HCC. BackgroundHepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide [1].Although improvements in many therapeutic strategies, including surgical resection, liver transplantation, and radiofrequency ablation, have improved the 5-year survival rate of HCC patients, its prognosis remains unsatisfactory [2]. Survival is associated with the use of targeted treatments, such as the tyrosine kinase inhibitor sorafenib, in patients with advanced stage cancer with vascular invasion and distant metastasis [3,4]. Clarifying the biological processes and molecular mechanisms

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“…Apoptosis of RPE cells caused by blue light plays an essential role in retinal photodamage, such as calcium homeostasis, mitochondrial damage, metabolic abnormalities, and oxidative damage [7] .The mitogen-activated protein kinase (MAPK) signaling pathway regulates multiple processes such as cell proliferation, survival, differentiation and apoptosis, and is activated by upstream kinases like the protein kinase C (PKC) [8,9] . A study about the role of fucoidan in diabetic retinopathy (DR) indicated that fucoidan could protect ARPE-19 cells against high glucose-induced oxidative damage involving the Ca 2+ -dependent ERK signaling pathway [10].…”

Section: Introductionmentioning

confidence: 99%

TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK

2020

Preprint

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Background Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of TRPM7 in photo-damaged RPE cells. Methods RPE cells isolated from Sprague-Dawley (SD) rats were cultured in vitro , and exposed to varying intensities of blue light (500-5000 Lux). Cell proliferation and viability were respectively assessed by BrdU incorporation and MTT assays. Real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of TRPM7, PKC, ERK and Bax/Bcl-2. The cells were transfected with TRPM7 siRNA to knockdown its mRNA levels, or transduced with TRPM7–overexpressing lentiviruses. Pigment epithelium-derived factor (PEDF) was used in combination to detect the anti apoptosis effect. Results Blue light inhibited the proliferation and viability of RPE cells in an intensity-de pendent manner when compared to non-irradiated controls ( P <0.05). Compared to the control, photo-damaged RPE cells showed decreased levels of TRPM7, PKC, ERK and Bax, increased in Bcl-2 ( P <0.01) . Forced expression of TRPM7 partially ameliorated the reduction of proliferation and viability of RPE cells( P <0.01), alleviated the downregulation of TRPM7, PKC, ERK and Bax expression levels( P <0.01), induced by blue light irradiation, while TRPM7 knockdown had opposite effects( P <0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light. Conclusions The apoptosis of RPE cells induced by blue light was positively correlated with the expression of TRPM7. Forced expression of TRPM7 partially attenuated the deleterious effects of blue-light-demaged RPE cells and showed a synergistic protective effect with PEDF, involving PKC/ERK signaling pathway.

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RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression

Cited by 191 publications

References 99 publications

Characterization of Bovine Neutrophil Extracellular Traps Induced by Histamine

Characterization of Bovine Neutrophil Extracellular Traps Induced by Histamine

TMEM147 promotes hepatocellular carcinoma progress by inducing EGFR/MAPK activity

TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK

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