Chlorogenic Acid Prevents AMPA-Mediated Excitotoxicity in Optic Nerve Oligodendrocytes Through a PKC and Caspase-Dependent Pathways

Autor:	Olfa Rebai, Mohamed Amri
Rok vydání:	2018
Předmět:	0301 basic medicine endocrine system Cell Survival Iron Excitotoxicity Caspase 3 AMPA receptor Toxicology medicine.disease_cause Neuroprotection Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Excitatory Amino Acid Agonists medicine Animals Enzyme Inhibitors Rats Wistar alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Cells Cultured Protein Kinase C Caspase biology Chemistry General Neuroscience Glutamate receptor Optic Nerve Hydrogen Peroxide Oligodendrocyte Mitochondria Rats Cell biology Oligodendroglia 030104 developmental biology medicine.anatomical_structure Animals Newborn Apoptosis Caspases biology.protein Chlorogenic Acid Reactive Oxygen Species 030217 neurology & neurosurgery Signal Transduction
Zdroj:	Neurotoxicity Research. 34:559-573
ISSN:	1476-3524 1029-8428
DOI:	10.1007/s12640-018-9911-5
Popis:	In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities. Chlorogenic acid (CGA) has been demonstrated to possess potent neuroprotective activities against oxidative stress in various cellular models and pathological conditions. Hence, CGA protect against oxidative stress and excitotoxic insults mediated by AMPA receptors and that the protective mechanisms involve free radical scavenging, Ca2+ handling in the cytosol, and modulating antioxidant enzyme system. CGA was associated with the protein kinase A (PKC) signaling pathways transduction. Caspases and calpains have been studied as apoptotic mediators and cell death in this model of AMPA toxicity. Inhibitors of caspases initiators, caspases 1, 8, and 9, the upstream of caspase 3 effectors, have totally abrogated the protective activity of CGA. Inhibitors of calpains also totally abrogated the protective activity of CGA. In addition, a potential role for the CGA in inhibiting Bax in oligodendrocyte cell model undergoing AMPA is inducing excitotoxic death. Our results indicate that CGA exhibits a protective potential via antioxidant and apoptosis caspases and calpains dependent against AMPA-mediated excitotoxicity, and these finding indicate that CGA is able to be a good candidate for preventive approach for neurodegenerative disorders associated with loss and damage in oligodendrocytes and AMPA-mediated excitotoxicity.
Databáze:	OpenAIRE
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