Inhibition of hydrogen peroxide-induced endothelial apoptosis by 2',4',7-trihydroxyflavanone, a flavonoid form.
Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion episodes. Oxidative injury can induce cellular and subcellular damage that results in apoptotic cell death. We tested whether 2',4',7-trihydroxyflavanone, a synthetic flavonoid derivative, inhibits hydrogen peroxide (H(2)O(2))-induced toxicity in human umbilical endothelial cells (HUVECs). Cultured HUVECs were incubated for 30 minutes with 0.2 mM H(2)O(2) in the absence and presence of 2',4',7-trihydroxyflavanone at a non-toxic concentration of 50 microM. The effect of 2',4',7-trihydroxyflavanone on apoptosis parameters was compared with that of naringenin and two flavonol derivatives, 2',4',7-trihydroxyflavonol and 2',4',6-trihydroxyflavonol. H(2)O(2) induced cell death within 24 hours over the range of 0.05-1.0 mM, and decreased cell viability by approximately 30% at 0.2 mM. This cytotoxicity was associated with nuclear condensation and DNA fragmentation, indicating induction of apoptosis. 2',4',7-Trihydroxyflavanone, as well as naringenin, was effective as an inhibitor of oxidative stress, protecting cell viability with >/=85% viable cells compared with the control, and no apparent nuclear condensation or DNA fragmentation. In contrast, the flavonol derivatives had no such effect. In addition, immunocytochemical data and Western blot analysis revealed that, unlike flavonol derivatives, the expression of Bcl-2 was markedly up-regulated, and that the expression of Bax and activation of caspase-3 were strongly inhibited by this flavanone derivative, thereby implicating antioxidant activity-related anti-apoptotic mechanisms of 2',4',7-trihydroxyflavanone. These results indicate that the synthetic flavonoid derivative 2',4',7-trihydroxyflavanone is an effective antioxidant, preventing endothelial apoptosis induced by H(2)O(2).
Choi
Yean-Jung
YJ
Division of Life Sciences, Hallym University, Chuncheon, Republic of Korea.
Lee
Myung-Kyu
MK
Lee
Yong-Jin
YJ
Jeong
Yu-Jin
YJ
Yoon Park
Jung Han
JH
Sung Lim
Soon
S
Kang
Young-Hee
YH
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000975:Antioxidants; C494826:BAX protein, human; D044950:Flavanones; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C005273:naringenin