scholarly journals Differential Activation of Glioprotective Intracellular Signaling Pathways in Primary Optic Nerve Head Astrocytes after Treatment with Different Classes of Antioxidants

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 324 ◽  
Author(s):  
Anita K. Ghosh ◽  
Vidhya R. Rao ◽  
Victoria J. Wisniewski ◽  
Alexandra D. Zigrossi ◽  
Jamie Floss ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Cell Viability ◽  
Optic Nerve Head ◽  
Intracellular Signaling ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glaucomatous Optic Neuropathy ◽  
Related Factor ◽  
Expression Levels ◽  
Reactive Astrocytosis

Optic nerve head astrocytes are the specialized glia cells that provide structural and trophic support to the optic nerve head. In response to cellular injury, optic nerve head astrocytes undergo reactive astrocytosis, the process of cellular activation associated with cytoskeletal remodeling, increases in the rate of proliferation and motility, and the generation of Reactive Oxygen Species. Antioxidant intervention has previously been proposed as a therapeutic approach for glaucomatous optic neuropathy, however, little is known regarding the response of optic nerve head astrocytes to antioxidants under physiological versus pathological conditions. The goal of this study was to determine the effects of three different antioxidants, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), resveratrol and xanthohumol in primary optic nerve head astrocytes. Effects on the expression of the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2), the antioxidant enzyme, manganese-dependent superoxide dismutase 2 (SOD2), and the pro-oxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), were determined by quantitative immunoblotting. Furthermore, efficacy in preventing chemically and reactive astrocytosis-induced increases in cellular oxidative stress was quantified using cell viability assays. The results were compared to the effects of the prototypic antioxidant, Trolox. Antioxidants elicited highly differential changes in the expression levels of Nrf2, SOD2, and NOX4. Notably, Mn-TM-2-PyP increased SOD2 expression eight-fold, while resveratrol increased Nrf2 expression three-fold. In contrast, xanthohumol exerted no statistically significant changes in expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake and lactate dehydrogenase (LDH) release assays were performed to assess cell viability after chemically and reactive astrocytosis-induced oxidative stress. Mn-TM-2-PyP exerted the most potent glioprotection by fully preventing the loss of cell viability, whereas resveratrol and xanthohumol partially restored cell viability. Our data provide the first evidence for a well-developed antioxidant defense system in optic nerve head astrocytes, which can be pharmacologically targeted by different classes of antioxidants.

scholarly journals Inhibition of cAMP/PKA Pathway Protects Optic Nerve Head Astrocytes against Oxidative Stress by Akt/Bax Phosphorylation-Mediated Mfn1/2 Oligomerization

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Won-Kyu Ju ◽  
Myoung Sup Shim ◽  
Keun-Young Kim ◽  
Tae Lim Park ◽  
Sangphil Ahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Protein Expression ◽  
Cell Viability ◽  
Optic Nerve Head ◽  
Mitochondrial Dynamics ◽  
Nerve Degeneration ◽  
Scanning Electron Microscopy Data ◽  
Pka Pathway ◽  
The Impact

Glaucoma is characterized by a progressive optic nerve degeneration and retinal ganglion cell loss, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role in glaucomatous neurodegeneration. Here, we investigate the impact of activation of cyclic adenosine 3′,5′-monophosphate (cAMP)/protein kinase A (PKA) pathway on mitochondrial dynamics of ONH astrocytes exposed to oxidative stress. ONH astrocytes showed a significant loss of astrocytic processes in the glial lamina of glaucomatous DBA/2J mice, accompanied by basement membrane thickening and collagen deposition in blood vessels and axonal degeneration. Serial block-face scanning electron microscopy data analysis demonstrated that numbers of total and branched mitochondria were significantly increased in ONH astrocytes, while mitochondrial length and volume density were significantly decreased. We found that hydrogen peroxide- (H2O2-) induced oxidative stress compromised not only mitochondrial bioenergetics by reducing the basal and maximal respiration but also balance of mitochondrial dynamics by decreasing dynamin-related protein 1 (Drp1) protein expression in rat ONH astrocytes. In contrast, elevated cAMP by dibutyryl-cAMP (dbcAMP) or isobutylmethylxanthine treatment significantly increased Drp1 protein expression in ONH astrocytes. Elevated cAMP exacerbated the impairment of mitochondrial dynamics and reduction of cell viability to oxidative stress in ONH astrocytes by decreasing optic atrophy type 1 (OPA1), and mitofusin (Mfn)1/2 protein expression. Following combined treatment with H2O2 and dbcAMP, PKA inhibition restored mitochondrial dynamics by increasing mitochondrial length and decreasing mitochondrial number, and this promoted cell viability in ONH astrocytes. Also, PKA inhibition significantly promoted Akt/Bax phosphorylation and Mfn1/2 oligomerization in ONH astrocytes. These results suggest that modulation of the cAMP/PKA signaling pathway may have therapeutic potential by activating Akt/Bax phosphorylation and promoting Mfn1/2 oligomerization in glaucomatous ONH astrocytes.

scholarly journals Integrins in Trabecular Meshwork and Optic Nerve Head: Possible Association with the Pathogenesis of Glaucoma

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yisheng Zhong ◽  
Jing Wang ◽  
Xunda Luo
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Trabecular Meshwork ◽  
Intracellular Signaling ◽  
Open Angle Glaucoma ◽  
Glaucomatous Optic Neuropathy ◽  
Stress And Strain ◽  
Membrane Spanning

Integrins are a family of membrane-spanning proteins that are important receptors for cell adhesion to extracellular matrix proteins. They also provide connections between the extracellular environment and intracellular cytoskeletons and are responsible for activation of many intracellular signaling pathways. In vitro and in vivo data strongly indicate that integrin-mediated signaling events can modulate the organization of the actin cytoskeleton in trabecular meshwork (TM) cells and are associated with astrocyte migration and microglia activation of the optic nerve head in patients with primary open angle glaucoma. Consequently, increase in resistance in the TM outflow pathways and remodeling of the optic nerve head occur, which in turn increases intraocular pressure (IOP), adds additional mechanical stress and strain to optic nerve axons, and accelerates damage of axons initially caused by optic nerve head remodeling. Integrins appear to be ideal candidates for translating physical stress and strain into cellular responses known to occur in glaucomatous optic neuropathy.

Parapapillary atrophy in optic neuropathies: Histology and clinical relevance

2021 ◽  
pp. 112067212110606
Author(s):  
Ana Banc ◽  
Stefania Bianchi Marzoli
Keyword(s):  
Optic Nerve ◽  
Optic Neuropathy ◽  
Optic Nerve Head ◽  
Clinical Findings ◽  
Age Related Macular Degeneration ◽  
Glaucomatous Optic Neuropathy ◽  
Age Related ◽  
High Resolution Images ◽  
Parapapillary Atrophy ◽  
Optic Nerve Disorders

Parapapillary atrophy is one of the parameters of the optic nerve head area which are assessed during the ophthalmoscopic examination particularly useful to characterize glaucomatous optic neuropathy. Optical coherence tomography evaluation provides high-resolution images of the optic nerve head and surrounding area, and can be used to study parapapillary atrophy. Different parapapillary atrophy zones were described depending on their histological features and research has been conducted to investigate the possible association between the presence and/ or size of parapapillary atrophy zones and several optic nerve disorders. In this review we discuss the histology and the clinical findings related to parapapillary atrophy in patients with glaucomatous optic neuropathy, non-glaucomatous optic neuropathies (e.g. arteritic and non-arteritic anterior ischemic optic neuropathies; suprasellar and parasellar tumors), and other ocular conditions (e.g. high myopia; age-related macular degeneration). Two different histologic classifications were identified. Parapapillary atrophy was demonstrated in glaucoma and glaucoma-like neuropathies, but not in other types of optic nerve disorders.

scholarly journals Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fabiola Cortes-Lopez ◽  
Alicia Sanchez-Mendoza ◽  
David Centurion ◽  
Luz G. Cervantes-Perez ◽  
Vicente Castrejon-Tellez ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Glucose ◽  
Cardiac Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Irreversible Damage ◽  
Peroxisome Proliferator Activated Receptor ◽  
Subunit Expression ◽  
Endothelial Nitric Oxide

Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte.

scholarly journals The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 610 ◽  
Author(s):  
Yanzhuo Kong ◽  
Kenneth J. Olejar ◽  
Stephen L. W. On ◽  
Venkata Chelikani
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Pathogenic Microorganisms ◽  
Gi Tract ◽  
Lactobacillus Spp

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI tract is usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms and dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role in modulating oxidative stress in cells and tissues, especially in the GI tract. Oxidative stress is linked with excessive reactive oxygen species (ROS) that can be formed by a few enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). The redox mechanisms of Lactobacillus spp. may contribute to the downregulation of these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf-2) and nuclear factor kappa B (NF-κB) are two common transcription factors, through which Lactobacillus spp. modulate oxidative stress as well. As oxidative stress is closely associated with inflammation and certain diseases, Lactobacillus spp. could potentially be applied for early treatment and amelioration of these diseases, either individually or together with prebiotics. However, further research is required for revealing their mechanisms of action as well as their extensive application in the future.

scholarly journals Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes

2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Myoung Sup Shim ◽  
Keun-Young Kim ◽  
Jung Hyun Bu ◽  
Hye Seung Nam ◽  
Seung Won Jeong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Nerve Head ◽  
Intracellular Camp

scholarly journals Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes

2015 ◽  
Vol 138 ◽  
pp. 159-166 ◽  
Author(s):  
Simon Kaja ◽  
Andrew J. Payne ◽  
Yuliya Naumchuk ◽  
Deborah Levy ◽  
Danish H. Zaidi ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Cell Viability ◽  
Optic Nerve Head ◽  
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