Puerarin attenuates angiotensin II-induced cardiac fibroblast proliferation via the promotion of catalase activity and the inhibition of hydrogen peroxide-dependent Rac-1 activation / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
; (6): 41-52, 2018.
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| ID: wpr-773640
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WPRO
ABSTRACT
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 HO 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 Rac1 was dependent on the levels of intracellular HO. 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 HO-dependent Rac1 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 downregulation of catalase expression and HO-dependent Rac1 activation.
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Asunto principal:
Farmacología
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Neuropéptidos
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Angiotensina II
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Transducción de Señal
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Catalasa
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Activación Transcripcional
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Células Cultivadas
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Regulación de la Expresión Génica
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Factor de Transcripción AP-1
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NADPH Oxidasas
Límite:
Animals
Idioma:
En
Revista:
Chinese Journal of Natural Medicines (English Ed.)
Año:
2018
Tipo del documento:
Article