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Glutamoyl diester of the dietary polyphenol curcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondria in vitro: implications for Parkinson's disease.
Mol Cell Biochem. 2011 Jan; 347(1-2):135-43.MC

Abstract

Oxidative/nitrosative stress plays a crucial role in Parkinson's disease (PD) by triggering mitochondrial dysfunction. Nitrosative stress is mediated by reactive species such as peroxynitrite (PN) which could damage biomolecules thereby impinging on the cellular machinery. We observed that PN (0-1000 μM) inhibited brain mitochondrial complex I (CI) activity in a dose-dependent manner with concomitant tyrosine nitration of proteins. We also observed that exposure to PN at low concentrations (62.5-125 μM) significantly decreased the mitochondrial membrane potential and affected the mitochondrial integrity at higher doses (500-750 μM) as indicated by the mitochondrial swelling experiment. Therefore, it could be surmised that compounds that prevent such mitochondrial damage might have therapeutic value in neurological conditions such as PD. We previously showed that curcumin could detoxify PN and protect against CI inhibition and protein nitration. However, the therapeutic potential of curcumin is constrained by limited bioavailability. To address this issue and obtain improved antioxidants, three bioconjugates of curcumin (Di-demethylenated piperoyl, di-valinoyl and di-glutamoyl esters) were generated and tested against PN-mediated nitrosative stress and mitochondrial damage. We found that among the bioconjugates, the glutamoyl diester of curcumin showed improved protection against PN-dependent CI inhibition and protein nitration compared to other conjugates. Di-glutamoyl curcumin protected dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP(+))-mediated neuronal death. These effects were improved compared to curcumin alone suggesting that di-glutamoyl curcumin could be a better neuroprotective agent in neurodegenerative diseases such as PD.

Authors+Show Affiliations

Department of Neurochemistry, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore, 560029, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20972609

Citation

Mythri, Rajeswara Babu, et al. "Glutamoyl Diester of the Dietary Polyphenol Curcumin Offers Improved Protection Against Peroxynitrite-mediated Nitrosative Stress and Damage of Brain Mitochondria in Vitro: Implications for Parkinson's Disease." Molecular and Cellular Biochemistry, vol. 347, no. 1-2, 2011, pp. 135-43.
Mythri RB, Harish G, Dubey SK, et al. Glutamoyl diester of the dietary polyphenol curcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondria in vitro: implications for Parkinson's disease. Mol Cell Biochem. 2011;347(1-2):135-43.
Mythri, R. B., Harish, G., Dubey, S. K., Misra, K., & Bharath, M. M. (2011). Glutamoyl diester of the dietary polyphenol curcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondria in vitro: implications for Parkinson's disease. Molecular and Cellular Biochemistry, 347(1-2), 135-43. https://doi.org/10.1007/s11010-010-0621-4
Mythri RB, et al. Glutamoyl Diester of the Dietary Polyphenol Curcumin Offers Improved Protection Against Peroxynitrite-mediated Nitrosative Stress and Damage of Brain Mitochondria in Vitro: Implications for Parkinson's Disease. Mol Cell Biochem. 2011;347(1-2):135-43. PubMed PMID: 20972609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutamoyl diester of the dietary polyphenol curcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondria in vitro: implications for Parkinson's disease. AU - Mythri,Rajeswara Babu, AU - Harish,G, AU - Dubey,Shiv Kumar, AU - Misra,Krishna, AU - Bharath,M M Srinivas, Y1 - 2010/10/23/ PY - 2010/07/09/received PY - 2010/10/06/accepted PY - 2010/10/26/entrez PY - 2010/10/26/pubmed PY - 2011/3/29/medline SP - 135 EP - 43 JF - Molecular and cellular biochemistry JO - Mol Cell Biochem VL - 347 IS - 1-2 N2 - Oxidative/nitrosative stress plays a crucial role in Parkinson's disease (PD) by triggering mitochondrial dysfunction. Nitrosative stress is mediated by reactive species such as peroxynitrite (PN) which could damage biomolecules thereby impinging on the cellular machinery. We observed that PN (0-1000 μM) inhibited brain mitochondrial complex I (CI) activity in a dose-dependent manner with concomitant tyrosine nitration of proteins. We also observed that exposure to PN at low concentrations (62.5-125 μM) significantly decreased the mitochondrial membrane potential and affected the mitochondrial integrity at higher doses (500-750 μM) as indicated by the mitochondrial swelling experiment. Therefore, it could be surmised that compounds that prevent such mitochondrial damage might have therapeutic value in neurological conditions such as PD. We previously showed that curcumin could detoxify PN and protect against CI inhibition and protein nitration. However, the therapeutic potential of curcumin is constrained by limited bioavailability. To address this issue and obtain improved antioxidants, three bioconjugates of curcumin (Di-demethylenated piperoyl, di-valinoyl and di-glutamoyl esters) were generated and tested against PN-mediated nitrosative stress and mitochondrial damage. We found that among the bioconjugates, the glutamoyl diester of curcumin showed improved protection against PN-dependent CI inhibition and protein nitration compared to other conjugates. Di-glutamoyl curcumin protected dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP(+))-mediated neuronal death. These effects were improved compared to curcumin alone suggesting that di-glutamoyl curcumin could be a better neuroprotective agent in neurodegenerative diseases such as PD. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/20972609/Glutamoyl_diester_of_the_dietary_polyphenol_curcumin_offers_improved_protection_against_peroxynitrite_mediated_nitrosative_stress_and_damage_of_brain_mitochondria_in_vitro:_implications_for_Parkinson's_disease_ L2 - https://doi.org/10.1007/s11010-010-0621-4 DB - PRIME DP - Unbound Medicine ER -