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Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells.
Mol Cell Biochem. 2015 Nov; 409(1-2):199-211.MC

Abstract

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

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.

Authors+Show Affiliations

Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India.Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India. sudhandiran@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26280522

Citation

Kulasekaran, Gopinath, and Sudhandiran Ganapasam. "Neuroprotective Efficacy of Naringin On 3-nitropropionic Acid-induced Mitochondrial Dysfunction Through the Modulation of Nrf2 Signaling Pathway in PC12 Cells." Molecular and Cellular Biochemistry, vol. 409, no. 1-2, 2015, pp. 199-211.
Kulasekaran G, Ganapasam S. Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. Mol Cell Biochem. 2015;409(1-2):199-211.
Kulasekaran, G., & Ganapasam, S. (2015). Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. Molecular and Cellular Biochemistry, 409(1-2), 199-211. https://doi.org/10.1007/s11010-015-2525-9
Kulasekaran G, Ganapasam S. Neuroprotective Efficacy of Naringin On 3-nitropropionic Acid-induced Mitochondrial Dysfunction Through the Modulation of Nrf2 Signaling Pathway in PC12 Cells. Mol Cell Biochem. 2015;409(1-2):199-211. PubMed PMID: 26280522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. AU - Kulasekaran,Gopinath, AU - Ganapasam,Sudhandiran, Y1 - 2015/08/18/ PY - 2015/02/16/received PY - 2015/08/06/accepted PY - 2015/8/18/entrez PY - 2015/8/19/pubmed PY - 2016/7/23/medline KW - 3-Nitropropionic acid KW - Apoptosis KW - Mitochondrial dysfunction KW - Naringin KW - Nrf2 KW - Oxidative stress KW - PI-3K/Akt SP - 199 EP - 211 JF - Molecular and cellular biochemistry JO - Mol Cell Biochem VL - 409 IS - 1-2 N2 - UNLABELLED: 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 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. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/26280522/Neuroprotective_efficacy_of_naringin_on_3_nitropropionic_acid_induced_mitochondrial_dysfunction_through_the_modulation_of_Nrf2_signaling_pathway_in_PC12_cells_ L2 - https://doi.org/10.1007/s11010-015-2525-9 DB - PRIME DP - Unbound Medicine ER -