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

2020 ◽  
Vol 2020 ◽  
pp. 1-2
Author(s):  
Won-Kyu Ju ◽  
Myoung Sup Shim ◽  
Keun-Young Kim ◽  
Tae Lim Park ◽  
Sangphil Ahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Nerve Head ◽  
Pka Pathway

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 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 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

Oxidative Stress and TGF-β2 Increase Heat Shock Protein 27 Expression in Human Optic Nerve Head Astrocytes

2008 ◽  
Vol 49 (12) ◽  
pp. 5403 ◽  
Author(s):  
Alice L. Yu ◽  
Rudolf Fuchshofer ◽  
Marco Birke ◽  
Anselm Kampik ◽  
Hans Bloemendal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Optic Nerve Head ◽  
Heat Shock Protein 27 ◽  
Human Optic Nerve

scholarly journals Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

2013 ◽  
Vol 22 (5) ◽  
pp. 404-412 ◽  
Author(s):  
Marcus Kernt ◽  
Nicole Arend ◽  
Alexandra Buerger ◽  
Thomas Mann ◽  
Christos Haritoglou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Nerve Head ◽  
Human Optic Nerve
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