Cell Type-Specific Upregulation of Parkin in Response to ER Stress

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Abstract
Parkin is the gene responsible for a familial form of Parkinson's disease (PD) termed autosomal recessive juvenile parkinsonism (AR-JP)/PARK2. Parkin has been shown to protect cells from endoplasmic reticulum (ER) stress and oxidative stress, presumably due to its ubiquitin ligase (E3) activity that targets proteins for proteasomal degradation. Although the authors showed that parkin is upregulated in response to ER stress, subsequent reports suggest that it does not represent a universal unfolded protein response (UPR). Here the authors report different regulation of parkin in response to ER stress in different cell lines, demonstrating upregulation of parkin as a cell type-specific response to ER stress. 2-Mercaptoethanol (2-ME) and tunicamycin increased the expression of parkin in SH-SY5Y (H) cells, Neuro2a cells, Goto-P3 cells, but not in SH-SY5Y (J) cells and IMR32 cells. In parallel with these studies, similar upregulation of the parkin coregulated gene (PACRG)/gene adjacent to parkin (Glup) was also observed by ER stress. Luciferase assays failed to detect the transcriptional activation of 500 bp parkin/Glup promoter in response to ER stress. These results indicate that induction of parkin by ER stress represents a cell type-specific response.