TY - JOUR
T1 - Butin (7,3′,4′-trihydroxydihydroflavone) reduces oxidative stress-induced cell death via inhibition of the mitochondria-dependent apoptotic pathway
AU - Zhang, Rui
AU - Lee, In Kyung
AU - Piao, Mei Jing
AU - Kim, Ki Cheon
AU - Kim, Areum Daseul
AU - Kim, Hye Sun
AU - Chae, Sungwook
AU - Kim, Hee Sun
AU - Hyun, Jin Won
PY - 2011/6
Y1 - 2011/6
N2 - Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H 2O 2)-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 H 2O 2-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 H 2O 2 treatment. Finally, butin exhibited protective effects against H 2O 2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G 1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H 2O 2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.
AB - Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H 2O 2)-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 H 2O 2-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 H 2O 2 treatment. Finally, butin exhibited protective effects against H 2O 2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G 1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H 2O 2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.
KW - Butin
KW - Mitochondria-dependent apoptotic pathway
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=79959698310&partnerID=8YFLogxK
U2 - 10.3390/ijms12063871
DO - 10.3390/ijms12063871
M3 - Article
C2 - 21747713
AN - SCOPUS:79959698310
SN - 1661-6596
VL - 12
SP - 3871
EP - 3887
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
ER -