Chlorogenic Acid Prevents AMPA-Mediated Excitotoxicity in Optic Nerve Oligodendrocytes Through a PKC and Caspase-Dependent Pathways
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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.
KeywordsAMPA excitotoxicity Oligodendrocyte ROS Chlorogenic acid PKC Antioxidant enzymes Apoptosis pathway
Reactive oxygen species
Central nervous system
System nervous peripheral
Protein kinase A
Protein kinase C
Mitogen apoptotic protein kinase
Hank’s balanced salt solution
Amyotrophic lateral sclerosis
We would like to thank Professor Matute Carlos and Sanchez-Gomez Maria Victoria as well as all the members of the Departamento de Neurociencias, Facultad de Medicina y Odontologia, Universidad Del Paıs Vasco, Leioa, Vizcaya, Spain, for their supportive advices.
This work was supported by the Research Unit 00-UR-08-01University of Sciences Tunis and by a grant from the Tunisian Ministry of Higher Education and Scientific Research Tunisia.
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