Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: protection by N-acetyl-l-cysteine

The goals of this study were to evaluate the effects of ionizing radiation on apical junctions in colonic epithelium and mucosal barrier function in mice in vivo. Adult mice were subjected to total body irradiation (4 Gy) with or without N-acetyl-l-cysteine (NAC) feeding for 5 days before irradiation. At 2–24 h postirradiation, the integrity of colonic epithelial tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton was assessed by immunofluorescence microscopy and immunoblot analysis of detergent-insoluble fractions for TJ and AJ proteins. The barrier function was evaluated by measuring vascular-to-luminal flux of fluorescein isothiocyanate (FITC)-inulin in vivo and luminal-to-mucosal flux in vitro. Oxidative stress was evaluated by measuring protein thiol oxidation. Confocal microscopy showed that radiation caused redistribution of occludin, zona occludens-1, claudin-3, E-cadherin, and β-catenin, as well as the actin cytoskeleton as early as 2 h postirradiation, and this effect was sustained for at least 24 h. Feeding NAC before irradiation blocked radiation-induced disruption of TJ, AJ, and the actin cytoskeleton. Radiation increased mucosal permeability to inulin in colon, which was blocked by NAC feeding. The level of reduced-protein thiols in colon was depleted by radiation with a concomitant increase in the level of oxidized-protein thiol. NAC feeding blocked the radiation-induced protein thiol oxidation. These data demonstrate that radiation rapidly disrupts TJ, AJ, and the actin cytoskeleton by an oxidative stress-dependent mechanism that can be prevented by NAC feeding.

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Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies

FEBS Journal ◽

10.1111/febs.12142 ◽

2013 ◽

Vol 280 (17) ◽

pp. 4149-4164 ◽

Cited By ~ 86

Author(s):

Jessica R. Terrill ◽

Hannah G. Radley-Crabb ◽

Tomohito Iwasaki ◽

Frances A. Lemckert ◽

Peter G. Arthur ◽

...

Keyword(s):

Oxidative Stress ◽

Muscular Dystrophies ◽

Thiol Oxidation ◽

Protein Thiol ◽

Protein Thiol Oxidation

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Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo

Chemico-Biological Interactions ◽

10.1016/j.cbi.2010.02.031 ◽

2010 ◽

Vol 185 (3) ◽

pp. 215-226 ◽

Cited By ~ 47

Author(s):

Kyoung Ah Kang ◽

Rui Zhang ◽

Sungwook Chae ◽

Su Jae Lee ◽

Jihoon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Ionizing Radiation ◽

Cell Damage ◽

Radiation Induced

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P4.22 In vivo decrease of elevated protein thiol oxidation and protection of dystrophic muscle from exercise induced damage, using the thiol containing antioxidant N-acetylcysteine in dystrophic mdx mice

Neuromuscular Disorders ◽

10.1016/j.nmd.2011.06.987 ◽

2011 ◽

Vol 21 (9-10) ◽

pp. 710-711

Author(s):

J.R. Terrill ◽

H.G. Radley-Crabb ◽

M.D. Grounds ◽

P.G. Arthur

Keyword(s):

Mdx Mice ◽

Thiol Oxidation ◽

Protein Thiol ◽

Dystrophic Muscle ◽

Elevated Protein ◽

Exercise Induced ◽

Protein Thiol Oxidation

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Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

10.21203/rs.3.rs-737962/v1 ◽

2021 ◽

Author(s):

Wei Hu ◽

Jiawu Liang ◽

Song Liao ◽

Zhidong Zhao ◽

Yuxing Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Flow Cytometry ◽

Genomic Stability ◽

Bone Defects ◽

Self Renewal ◽

Tnf Α ◽

Radiation Induced ◽

Γ Ray

Abstract Background Ionizing radiation poses a challenge to the healing of bone defects. Radiation therapy and accidental exposure to gamma-ray (γ-ray) radiation inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are essential for osteogenic lineages, bone maintenance, and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defects. Methods CBSCs were extracted from C57/BL6 mice and were identified by flow cytometry. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs were detected in vitro. The underlying mechanisms in terms of genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by western blotting, flow cytometry and immunofluorescence. Finally, the effects of melatonin on healing in postradiation bone defects were evaluated in vivo by micro-CT and immunohistochemical analysis. Results The radiation-induced reduced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin. Melatonin maintained the genomic stability and apoptosis of postradiation CBSCs, and intracellular oxidative stress was decreased significantly while antioxidant-related enzymes were enhanced. Western blotting verified the anti-inflammatory effect of melatonin by downregulating the levels of IL-6 and TNF-α via extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) signaling, distinct from its antioxidant effect via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density (BMD) values, and lower levels of IL-6 and TNF-α than those in the irradiation and the Matrigel groups. Conclusions This study suggested the potential of melatonin to protect CBSCs against γ-ray radiation and to assist the healing of postradiation bone defects.

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Cytosolic increased labile Zn2+ contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion

Journal of Trace Elements in Medicine and Biology ◽

10.1016/j.jtemb.2018.04.014 ◽

2018 ◽

Vol 48 ◽

pp. 202-212 ◽

Cited By ~ 9

Author(s):

Sinan Degirmenci ◽

Yusuf Olgar ◽

Aysegul Durak ◽

Erkan Tuncay ◽

Belma Turan

Keyword(s):

Action Potentials ◽

Left Ventricular ◽

Atp Depletion ◽

Thiol Oxidation ◽

Protein Thiol ◽

Ventricular Cardiomyocytes ◽

Protein Thiol Oxidation

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Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

Current Neuropharmacology ◽

10.2174/1570159x19666210524152817 ◽

2021 ◽

Vol 19 ◽

Author(s):

Tapan Behl ◽

Gagandeep Kaur ◽

Aayush Sehgal ◽

Gokhan Zengin ◽

Sukhbir Singh ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ionizing Radiation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Radiation Induced ◽

Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

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Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation

Cardiovascular Research ◽

10.1093/cvr/cvaa123 ◽

2020 ◽

Cited By ~ 10

Author(s):

Detmar Kolijn ◽

Steffen Pabel ◽

Yanna Tian ◽

Mária Lódi ◽

Melissa Herwig ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ejection Fraction ◽

Linear Regression Analysis ◽

Lipid Peroxide ◽

Dependent Manner ◽

Preserved Ejection Fraction ◽

Human Heart Failure ◽

Stress Dependent

Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods and results The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients. Conclusion Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO–sGC–cGMP–cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.

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