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KMID : 0043320180410101009
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Archives of Pharmacal Research
2018 Volume.41 No. 10 p.1009 ~ p.1018
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Paeoniflorin attenuates atRAL-induced oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress in retinal pigment epithelial cells via triggering Ca2+/CaMKII-dependent activation of AMPK
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Zhu Xue
Wang Ke
Zhou Fanfan
Zhu Ling
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Abstract
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Abnormal accumulation of the free-form all-trans-retinal (atRAL), a major intermediate of human visual cycle, is considered to be a key cause of retinal pigment epithelial (RPE) dysfunction in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration (AMD). Paeoniflorin (PF), a monoterpene glucoside isolated from Paeonia lactiflora Pall., has been used in clinical treatment of retinal degenerative diseases in China for several years; however, the underlying mechanism remains unclear. The aim of this study is to investigate the protective effect of PF against atRAL toxicity in human ARPE-19 cells and its molecular mechanism. The results of our study showed that the pre-treatment of PF dose-dependently attenuated atRAL-induced cell injury by the reduction of Nox1/ROS-associated oxidative stress, mitochondrial dysfunction and GRP78-PERK-eIF2α-ATF4-CHOP-regulated endoplasmic reticulum (ER) stress in ARPE-19 cells. Additionally, our data showed that PF mainly exerted its activity via triggering calcium-calmodulin dependent protein kinase II (CaMKII)-mediated activation of AMP-activated protein kinase (AMPK). AMPK inhibition significantly reversed the protective effect of PF against atRAL toxicity in ARPE-19 cells. Overall, our findings provided the novel mechanism of PF protecting human RPE cells, which may prevent the progression of retinal degenerative diseases.
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KEYWORD
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Paeoniflorin, All-trans-retinal, RPE, AMPK
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