caa a22 4500 606234845 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2525-9 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2525-9 Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells [Elektronische Daten] [Gopinath Kulasekaran, Sudhandiran Ganapasam] Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington's disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluatedthe by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the NAD(P)H:quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI-3K/Akt-dependent Nrf2 activation in PC12 cells. Springer Science+Business Media New York, 2015 Naringin nationallicence 3-Nitropropionic acid nationallicence Oxidative stress nationallicence Mitochondrial dysfunction nationallicence Apoptosis nationallicence Nrf2 nationallicence PI-3K/Akt nationallicence Kulasekaran Gopinath Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Ganapasam Sudhandiran Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 199-211 0300-8177 409:1-2<199 2015 409 11010 https://doi.org/10.1007/s11010-015-2525-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2525-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kulasekaran Gopinath Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Ganapasam Sudhandiran Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 199-211 0300-8177 409:1-2<199 2015 409 11010