FIG. 1.

Activation of ER stress after chronic IH. (A) Upregulation of Grp78, caspase-12, and CHOP after 14 days of IH treatment, which was prevented by the injection of TUDCA. (B) Shows the pooled data from four animals. One-way ANOVA [F(3, 12)=6.62, p<0.01 for Grp78; F(3, 12)=6.05, p<0.01 for caspase-12; F(3, 12)=4.53, p=0.02 for CHOP], followed by post hoc analysis with Newman–Keuls's test. (C) Significant alterations in ER ultrastructure were observed after 14 days of hypoxia/reoxygenation exposure. Most of the perinuclear ER (indicated by arrowheads) formed parallel sheets in CA1 pyramidal neurons in the control group (i) and TUDCA treatment (ii). In contrast, ERs in the IH group (iii) were swollen, distorted, and frequently misoriented, suggesting protein aggregation in the lumen. The inset in each picture is enlarged and displayed on the right. Treatment with TUDCA prevented the alteration in ER structure (iv). *p<0.05; **p<0.01; ns, not significant. Scale bars: 0.5 μm. ANOVA, analysis of variance; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; Grp78, glucose-regulated protein 78; IH, intermittent hypoxia; TUDCA, tauroursodeoxycholic acid.