The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nico...The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nicotinamide adenine dinucleotide phosphate （NADPH） oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac 1 was dependent on the levels of intracellular H202. Puerarin blocked the phosphorylation of extracellular regulated protein kinases （ERK）1/2, abolished activator protein （AP）-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H202-dependent Racl activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregu- lation of catalase expression and H202-dependent Racl activation.展开更多
基金supported by the National S&T Major Special Project on Major New Drug Innovation(No.2012ZX09301002-001-015)the National Natural Science Foundation of China(No.30772284)
文摘The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nicotinamide adenine dinucleotide phosphate （NADPH） oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac 1 was dependent on the levels of intracellular H202. Puerarin blocked the phosphorylation of extracellular regulated protein kinases （ERK）1/2, abolished activator protein （AP）-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H202-dependent Racl activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregu- lation of catalase expression and H202-dependent Racl activation.
