4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress in Chondrocytes That Is Caused by Loss of the Protein Disulfide Isomerase ERp57

Figure 3

4-PBA efficiently reduces various levels of ER stress in vitro. (a) Immunoblot analysis of micromass cultures of ERp57 KO and control cells to analyze ER marker proteins in the presence of 50 mM 4-PBA. Unstimulated C28/I2 cells served as control and their protein/GAPDH ratios were set at 1. As expected, BiP, Chop, and IRE1 are increased in ERp57 KO cells compared to the control cells in the absence of 4-PBA. The addition of 50 mM 4-PBA to ERp57 KO cells reduces ER stress marker protein expression levels to or even below control levels. , , , and . (b) Immunoblot analysis of micromass cultures of Thapsigargin- (Tg-) stimulated C28/I2 cells to analyze ER marker proteins in the presence of different concentrations of 4-PBA. Unstimulated C28/I2 cells served as control and their protein/GAPDH ratios were set as 1. As expected, BiP, Chop, ATF6, and ERp57 are increased in the presence of 10 μM Thapsigargin compared to the unstimulated control cells. The addition of 10, 20, and 50 mM 4-PBA to micromass cultures of Thapsigargin-stimulated C28/I2 cells dose-dependently reduced ER stress marker protein expression levels even under the control levels. , , , and .

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