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. 2016 Sep 8;1(14):e88797. doi: 10.1172/jci.insight.88797

Figure 4. Inhibition of ER stress protected against DOX-induced zebrafish death.

Figure 4

(A) Western blot (upper panel) and quantification (lower panel) analysis of glucose-regulated protein (Grp78) levels in adult WT fish heart at indicated time points after a single bolus of 20 μg/gram body mass (gbm) doxorubicin (DOX) injection. DOX injection results in elevation of Grp78 protein since 7 days after injection. Values are expressed relative to WT controls. Data represent mean ±SEM; *P < 0.05, 1-way ANOVA comparisons. (B) Western blot (upper) and quantification (lower) analysis of Grp78 protein levels at 2 months after DOX injection in indicated mutants and/or double-transgenic fish hearts. Grp78 protein level was further elevated in the GBT0411 mutant fish heart after DOX injection. Cardiomyocyte-specific overexpression of dnajb6b(L) inhibited the elevated ER stress in the GBT0411 mutant fish heart at 2 months after DOX injection. Values are expressed relative to WT controls. Data represent mean ±SEM; 1-way ANOVA comparisons, *P < 0.05. (C) Kaplan-Meier survival curves of indicated adult fish injected with a single bolus of 20 μg/gbm DOX with or without incubation with sodium phenylbutyrate (PBA), a chemical chaperone of ER stress inhibitor (250 μM, 10 hours/day, 5 days/week for the entire experiment). PBA administration protected against DOX-induced fish death in both WT and the GBT0411 mutant. *P < 0.05, log-rank test.