Oxidative stress and cell death: roles of PARP1 and AMPKWan-Wan LIN (National Taiwan University)
Invited by Benoit Viollet
Retinal pigment epithelium (RPE) located between the photoreceptors and the choroid is one of the major sites to arise oxidative stress in the eyes and is involved in phototoxicity and age-associated macular degeneration. We interest to investigate the death modes induced by UVA and methylglyoxal, a precursor of advanced glycation end products. We found UVA- and MGO-induced RPE cell death is protected by AMPK activators. UVA induces an autophagy-associated cell death which is resulting from the ROS/PARP-1/AMPK axis, and is balanced by the transactivation of EGFR.On the other hands, MGO inhibits AMPK activity, reduces autophagy, and induces mitochondrial fission. In addition, AMPK is involved to upregulate glyoxalase 1 that participates in the detoxification of MGO. We also found novel functions of CASK to mediate oxidative stress-induced cell death in RPE cells and retinal Müller cells.