Induction of Activating Transcription Factor 6 via Activation of ERK and ROS-P38 MAPK is Related to Methylglyoxal-Induced Cytotoxicity in Human Retinal Pigment Epithelial CellsEun Jung Park1, Young Sook Kim1,2, Nu Ri Kang1,2 and Jin Sook Kim1,2*
- Corresponding Author:
- Jin Sook Kim
Korean Medicine Convergence Research Division
Korea Institute of Oriental Medicine (KIOM)
1672 Yuseongdae-ro, Yuseong-gu, Daejeon 305-811, South Korea
Tel: 82-42-868- 9465
E-mail: [email protected]
Received Date: May 31, 2016; Accepted Date: July 08, 2016; Published Date: July 15, 2016
Citation: Park EJ, Kim YS, Kang NR, Kim JS (2016) Induction of Activating Transcription Factor 6 via Activation of ERK and ROS-P38 MAPK is Related to Methylglyoxal-Induced Cytotoxicity in Human Retinal Pigment Epithelial Cells. Biochem Pharmacol (Los Angel) 5:214. doi: 10.4172/2167-0501.1000214
Copyright: © 2016 Park EJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Methylglyoxal (MGO), a reactive α-oxoaldehyde produced by glucose metabolism, is elevated in several diabetic complications, including diabetic retinopathy. The breakdown of retinal pigment epithelial cells is implicated in the progression of diabetic retinopathy. Increased concentrations of MGO lead to retinal pigment epithelial cell death. In this study, we investigated the involvement of activating transcription factor 6 (ATF6) in MGO-mediated cytotoxicity in ARPE-19 cells. In response to high concentrations of MGO, unfolded protein response-related ATF6 was induced. Interestingly, the MGO also induced the generation of reactive oxygen species (ROS) and the phosphorylation of ERK and p38 MAPK. The induction of ATF6 was inhibited by ERK-specific and p38 MAPK-specific inhibitors (U0126 and SB202190) and by NAC, a well-known ROS scavenger. NAC also attenuated the phosphorylation of p38 MAPK. MGO induced cytotoxicity in the ARPE-19 cells, which was ameliorated by the inhibition of the ERK, p38 MAPK, and ROS pathways. Furthermore, the MGO-mediated cytotoxicity was inhibited by ATF6 siRNA. Taken together, these results clearly show that the induction of ATF6 via the ERK and ROS-p38 MAPK pathways is implicated in MGO-induced cytotoxicity in ARPE-19 cells.