Superoxide-hydrogen peroxide imbalance differentially modulates the keratinocytes cell line (HaCaT) oxidative metabolism via Keap1-Nrf2 redox signaling pathway

Abstract Insecticide resistance has recently become a serious problem in the agricultural field. Development of insecticides with new mechanisms of action is essential to overcome this limitation. Juvenile hormone (JH) is an insect-specific hormone that plays key roles in maintaining the larval stage of insects. Hence, JH signaling pathway is considered a suitable target in the development of novel insecticides; however, only a few JH signaling inhibitors (JHSIs) have been reported, and no practical JHSIs have been developed. Here, we established a high-throughput screening (HTS) system for exploration of novel JHSIs using a Bombyx mori cell line (BmN_JF&AR cells) and carried out a large-scale screening in this cell line using a chemical library. The four-step HTS yielded 69 compounds as candidate JHSIs. Topical application of JHSI48 to B. mori larvae caused precocious metamorphosis. In ex vivo culture of the epidermis, JHSI48 suppressed the expression of the Krüppel homolog 1 gene, which is directly activated by JH-liganded receptor. Moreover, JHSI48 caused a parallel rightward shift in the JH response curve, suggesting that JHSI48 possesses a competitive antagonist-like activity. Thus, large-scale HTS using chemical libraries may have applications in development of future insecticides targeting the JH signaling pathway.

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Novel and Converging Ways of NOX2 and SOD3 in Trafficking and Redox Signaling in Macrophages

Antioxidants ◽

10.3390/antiox10020172 ◽

2021 ◽

Vol 10 (2) ◽

pp. 172

Author(s):

Steen Vang Petersen ◽

Nanna Bach Poulsen ◽

Cecilie Linneberg Matthiesen ◽

Frederik Vilhardt

Keyword(s):

Hydrogen Peroxide ◽

Membrane Trafficking ◽

Spatial Organization ◽

Redox Signaling ◽

Small Gtpase ◽

Paracrine Signaling ◽

Tissue Macrophage ◽

Storage Vesicles ◽

Superoxide Dismutase 3 ◽

Macrophage Populations

Macrophages and related tissue macrophage populations use the classical NADPH oxidase (NOX2) for the regulated production of superoxide and derived oxidants for pathogen combat and redox signaling. With an emphasis on macrophages, we discuss how sorting into secretory storage vesicles, agonist-responsive membrane trafficking, and segregation into sphingolipid and cholesterol-enriched microdomains (lipid rafts) determine the subcellular distribution and spatial organization of NOX2 and superoxide dismutase-3 (SOD3). We discuss how inflammatory activation of macrophages, in part through small GTPase Rab27A/B regulation of the secretory compartments, mediates the coalescence of these two proteins on the cell surface to deliver a focalized hydrogen peroxide output. In interplay with membrane-embedded oxidant transporters and redox sensitive target proteins, this arrangement allows for the autocrine and paracrine signaling, which govern macrophage activation states and transcriptional programs. By discussing examples of autocrine and paracrine redox signaling, we highlight why formation of spatiotemporal microenvironments where produced superoxide is rapidly converted to hydrogen peroxide and conveyed immediately to reach redox targets in proximal vicinity is required for efficient redox signaling. Finally, we discuss the recent discovery of macrophage-derived exosomes as vehicles of NOX2 holoenzyme export to other cells.

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Protective effect of vanillic acid in hydrogen peroxide-induced oxidative stress in D.Mel-2 cell line

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2020.12.023 ◽

2020 ◽

Author(s):

Shagufta Taqvi ◽

Eijaz Ahmed Bhat ◽

Nasreena Sajjad ◽

Jamal S.M. Sabir ◽

Aleem Qureshi ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Protective Effect ◽

Cell Line ◽

Vanillic Acid

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Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1

PLoS ONE ◽

10.1371/journal.pone.0064372 ◽

2013 ◽

Vol 8 (5) ◽

pp. e64372 ◽

Cited By ~ 80

Author(s):

André Quincozes-Santos ◽

Larissa Daniele Bobermin ◽

Alexandra Latini ◽

Moacir Wajner ◽

Diogo Onofre Souza ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Cell Line ◽

Heme Oxygenase ◽

Heme Oxygenase 1

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859 poster Hydrogen peroxide enhances radiation-induced apoptosis in PC-3 prostate cancer cell line

Radiotherapy and Oncology ◽

10.1016/s0167-8140(04)82726-9 ◽

2004 ◽

Vol 73 ◽

pp. S366

Keyword(s):

Prostate Cancer ◽

Hydrogen Peroxide ◽

Cell Line ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Radiation Induced ◽

Induced Apoptosis

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Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽

10.1093/qjmed/hcab088.011 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Rowaida Mohammed Reda M. M Aboushahba ◽

Fayda Ibrahim Abdel Motaleb ◽

Ahmed Abdel Aziz Abou-Zeid ◽

Enas Samir Nabil ◽

Dalia Abdel-Wahab Mohamed ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Cell Line ◽

Signaling Pathway ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Wnt Signaling Pathway ◽

Control Group ◽

Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

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Abstract 017: Hyperglycemia-induced Posttranscriptional Modification Of Proinflammatory Cytokine Mrna Stability Is Mediated Via Hur/PKC-delta Signaling Pathway

Circulation Research ◽

10.1161/res.113.suppl_1.a017 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Suresh K Verma ◽

Alexander R Mackie ◽

Erin E Vaughan ◽

Tatiana V Abramova ◽

Raj kishore ◽

...

Keyword(s):

Mrna Expression ◽

Cell Line ◽

Signaling Pathway ◽

Mrna Stability ◽

Cardiac Fibrosis ◽

Diabetic Patients ◽

Tgf Beta ◽

Intramyocardial Injection ◽

Pkc Delta ◽

Increased Risk

Patients with diabetes are predisposed to increased risk of cardiovascular diseases. Persistent interaction of infiltrating macrophages and resident fibroblasts play a critical role in cardiac fibrosis. However, the signaling mechanism is not clear. We hypothesized that macrophage ELAV1 (mRNA stabilizing protein) modulates profibrotic mediators and extracellular matrix turnover by binding to 3′UTR and regulating the mRNA stability of TGF-beta and MMP-9 in hyperglycemic conditions. Mice receiving intramyocardial injection of HuR-specific shRNA showed significant reduction in infarct size and fibrosis area. Reduced fibrosis was associated with decrease in TGF-beta and MMP-9 expression in the myocardium. Conditioned media (CM) from high glucose (HG) treated macrophages significantly increased profibrogenic response (increased mRNA expression of Col1a1, Col3a1 and fibronectin) in fibroblast cell line as compared to fibroblasts incubated with CM from low glucose (LG)-treated macrophages. Knockdown of ELAV1 in HG-treated macrophages abrogated the profibrotic effects in fibroblasts. Indirect immunofluroscence of bone marrow-derived macrophages (BMM) demonstrated that HG increases nuclear ELAV1 export to the cytoplasm. Pharmacological inhibition of Protein kinase C-delta (PKCd) blocked HG-induced ELAV1 nuclear to cytoplasmic translocation. In vitro, stable knockdown of ELAV1 in mouse macrophage cell line RAW 264.7 reduced mRNA expression of TGF-beta and MMP-9 following LPS challenge, accompanied by a marked reduction in the mRNA stability of these genes. Our study here establishes an ELAV1/TGF-beta/MMP-9/PKC-delta signaling axis in the macrophages controlling the profibrogenic responses in fibroblasts, the major contributor in the pathogenesis of fibrosis. Therefore, targeting this signaling pathway might be of therapy value for cardiac fibrosis in diabetic patients.

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