Resveratrol Protects Optic Nerve Head Astrocytes from Oxidative Stress-Induced Cell Death by Preventing Caspase-3 Activation, Tau Dephosphorylation at Ser422 and Formation of Misfolded Protein Aggregates

Optic nerve head astrocytes (ONHAs) are the major cell type within the optic nerve head, providing both structural and nutrient support to the optic nerve. Astrocytes are necessary for the survival of neurons with controlled activation of astrocytes being beneficial to neurons. However, overactive a...

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Bibliographic Details
Published in:Cellular and molecular neurobiology 2020-08, Vol.40 (6), p.911-926
Main Authors: Means, John C., Lopez, Adam A., Koulen, Peter
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
Astrocytes
Biomedical and Life Sciences
Biomedicine
Butyl hydroperoxide
Caspase-3
Cell Biology
Cell death
Central nervous system
Cytoskeleton
Cytotoxicity
Dephosphorylation
Glaucoma
Inflammation
Nervous system
Neurobiology
Neurodegeneration
Neurodegenerative diseases
Neurofibrillary tangles
Neuroprotection
Neurosciences
Neurotoxicity
Optic nerve
Original Research
Oxidative stress
Protein folding
Proteolysis
Resveratrol
Retina
Structure-function relationships
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Summary:Optic nerve head astrocytes (ONHAs) are the major cell type within the optic nerve head, providing both structural and nutrient support to the optic nerve. Astrocytes are necessary for the survival of neurons with controlled activation of astrocytes being beneficial to neurons. However, overactive astrocytes can be harmful and the loss of normal astrocyte function can be a primary contributor to neurodegeneration. The neuroprotective properties of reactive astrocytes can be lost or they might gain neurotoxic properties in neurodegenerative diseases. The activated astrocytes are crucial in the development of glaucoma, where they serve as a source for cytotoxic substances that participate in ganglion apoptosis. There is increasing evidence indicating that neuroinflammation is an important process in glaucoma. Under pathological conditions, astrocytes can induce an inflammatory response. Extensive evidence shows that inflammatory responses mediated by astrocytes can also influence pathology development, synapse health, and neurodegeneration. The elimination of activated astrocytes by apoptosis is also expected in unfavorable conditions. In neurodegenerative diseases, a common feature is the presence of aggregates found in astrocytes, which can disrupt astrocyte function in such a way as to be detrimental to the viability of neurons. The biological processes involved in vision loss in glaucoma are not well understood. Despite the rapid advances in our understanding of optic nerve head (ONH) structure and function, numerous potential contributions of the ONHAs to optic nerve damage remain unanswered. The present study investigated the role of ONHAs during oxidative stress in order to determine novel cell biological processes underlying glaucoma pathogenesis. ONHAs were exposed to chemically induced oxidative stress using tert -butyl hydroperoxide ( t BHP) in order to model extracellular oxidative stress as it occurs in the glaucomatous retina and ONH. In order to determine the impact of an intervention approach employing potential glioprotective treatments for central nervous system tissue we pretreated cells with the polyphenolic phytostilbene and antioxidant trans -resveratrol (3,5,4′-trihydroxy- trans -stilbene). ONHAs exposed to t BHP-mediated oxidative stress displayed decreased viability and underwent apoptosis. In addition, increased levels of activated caspases, dephosphorylation of Tau protein at Ser 422 , an important site adjacent to the caspase clea
ISSN:0272-4340
1573-6830
DOI:10.1007/s10571-019-00781-6