2009年被美国“科学”杂志评为全球十大科学发现之一,是特异作用TOR(Target Of Rapamycin,TOR)的免疫抑制剂雷帕霉素(rapamycin)能明显地延长小鼠的寿命。这项激动人心的研究结果不仅使老年医学研究者进一步坚定了药物抗衰老的信心,同时也促使人们重新审视TOR信号通路与衰老的关系,
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.