Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells.
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 evaluated the 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
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.
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India.
Gopinath
G
Kulasekaran
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India. sudhandiran@yahoo.com.
Sudhandiran
S
Ganapasam
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000473:pathology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011422:Propionates / Q000633:toxicity*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000975:Antioxidants; D044950:Flavanones; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D009574:Nitro Compounds; D011422:Propionates; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; C005274:naringin; C015392:3-nitropropionic acid
3-Nitropropionic acid; Apoptosis; Mitochondrial dysfunction; Naringin; Nrf2; Oxidative stress; PI-3K/Akt