کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4324825 1613940 2013 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protective effect of lipoic acid against oxidative stress is mediated by Keap1/Nrf2-dependent heme oxygenase-1 induction in the RGC-5 cellline
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Protective effect of lipoic acid against oxidative stress is mediated by Keap1/Nrf2-dependent heme oxygenase-1 induction in the RGC-5 cellline
چکیده انگلیسی

Oxidative stress plays a key role in neurodegeneration of CNS neurons such as in Alzheimer disease, Parkinson's disease and glaucoma. R-α-lipoic acid (R-LA) has been shown to have a neuroprotective effect through its antioxidant activity. However, the mechanism underlying its neuroprotection is totally unknown in retinal neurons. In this study, we show that R-LA has a dramatic neuroprotective effect against oxidative stress-induced death of the retinal neuronal RGC-5 cell line. We observed that R-LA induces the expression of heme oxygenase-1 (HO-1) by promoting the translocation of NF-E2-related factor 2 (Nrf2) to the nucleus. We examined the mechanism underlying HO-1 induction by R-LA by focusing on downstream signaling pathways. We found that R-LA activates Akt, and HO-1 induction by R-LA (involving Nrf2 translocation to the nucleus) was suppressed by phosphoinositide 3-kinase (PI3K) inhibitors. In addition, R-LA produced reactive oxygen species (ROS), including hydrogen peroxide. Pretreatment with a ROS scavenger or a NADPH oxidase inhibitor suppressed R-LA-induced Nrf2 translocation to the nucleus and HO-1 induction. These results suggest that ROS production triggered by R-LA might modify Kelch-like ECH-associated protein (Keap1), which in turn induces HO-1 expression through the PI3K signaling pathway. Furthermore, R-LA significantly attenuated cell death and accumulation of 4-hydroxy-2-nonenal (4HNE) in the retina induced by optic nerve injury in vivo through an HO-1 activity-dependent mechanism. These data demonstrate for the first time that R-LA exerts a neuroprotective effect against oxidative stress in retinal neurons in vitro and in vivo by inducing HO-1 through Keap1/Nrf2 signaling.


► R-LA has a protective effect against oxidative stress in RGC-5 cells.
► R-LA induces expression of the antioxidant HO-1 in RGC-5 cells.
► R-LA induces PI3K-dependent translocation of Nrf2 to the nucleus.
► The trigger for Nrf2 activation is ROS production by R-LA.
► R-LA prevents RGC death and 4HNE accumulation via HO-1 induction after injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1499, 7 March 2013, Pages 145–157
نویسندگان
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