Int. J. Mol. Sci. 2011, 12(6), 3871-3887; doi:10.3390/ijms12063871
Article

Butin (7,3′,4′-Trihydroxydihydroflavone) Reduces Oxidative Stress-Induced Cell Death via Inhibition of the Mitochondria-Dependent Apoptotic Pathway

1,†email, 2,†email, 1email, 1email, 1email, 2email, 3email, 4email and 1,* email
Received: 7 April 2011; in revised form: 16 May 2011 / Accepted: 31 May 2011 / Published: 10 June 2011
(This article belongs to the Section Bioactives and Nutraceuticals)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H2O2)-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2'-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H2O2-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH2-terminal kinase (JNK) and activator protein-1 cascades induced by H2O2 treatment. Finally, butin exhibited protective effects against H2O2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H2O2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway
Keywords: butin; oxidative stress; mitochondria-dependent apoptotic pathway
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MDPI and ACS Style

Zhang, R.; Lee, I.K.; Piao, M.J.; Kim, K.C.; Kim, A.D.; Kim, H.S.; Chae, S.; Kim, H.S.; Hyun, J.W. Butin (7,3′,4′-Trihydroxydihydroflavone) Reduces Oxidative Stress-Induced Cell Death via Inhibition of the Mitochondria-Dependent Apoptotic Pathway. Int. J. Mol. Sci. 2011, 12, 3871-3887.

AMA Style

Zhang R, Lee IK, Piao MJ, Kim KC, Kim AD, Kim HS, Chae S, Kim HS, Hyun JW. Butin (7,3′,4′-Trihydroxydihydroflavone) Reduces Oxidative Stress-Induced Cell Death via Inhibition of the Mitochondria-Dependent Apoptotic Pathway. International Journal of Molecular Sciences. 2011; 12(6):3871-3887.

Chicago/Turabian Style

Zhang, Rui; Lee, In Kyung; Piao, Mei Jing; Kim, Ki Cheon; Kim, Areum Daseul; Kim, Hye Sun; Chae, Sungwook; Kim, Hee Sun; Hyun, Jin Won. 2011. "Butin (7,3′,4′-Trihydroxydihydroflavone) Reduces Oxidative Stress-Induced Cell Death via Inhibition of the Mitochondria-Dependent Apoptotic Pathway." Int. J. Mol. Sci. 12, no. 6: 3871-3887.

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