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. 2019 Apr 18;26(4):571–583.e6. doi: 10.1016/j.chembiol.2019.01.010

Figure 2.

Figure 2

Comparison of the Effects of ES1 and Its Analogs ES2, ES24, ESR35, and ES47 on Cell Ca2+ Homeostasis

(A) ES1 comprises an aromatic-rich domain and a domain that contains a 5-nitrofuran (5-NF) group. The ES1 analogs carry chemical modifications either in the aromatic domain (ES2, ES24) or in the 5-NF domain (ESR35, ES47).

(B and C) The effects of ES2 on cytosolic (B) and ER (C) Ca2+ were mild compared with those of ES1, while ES24 rapidly depleted ER Ca2+ producing a robust accumulation of Ca2+ in cytosol.

(D and E) ESR35 was ineffective at all and ES47 produced minute effects on cytosolic (D) and ER (E) Ca2+.

(F) The area under the curve for TG responses shown in (A) were measured by integrating time courses of [Ca2+]cyt between 1,200 and 1,800 s (post-TG AUC).

(G and H) Half-times were determined for [Ca2+]ER decays (G) after application of ES1, ES2, and ES24 (pre-TG t1/2) and (H) after the subsequent TG application in experiments shown in (C) (post-TG t1/2).

(I and J) The area under the curve of TG responses in the experiments shown in (D) (post-TG AUC) (I) and the half-time of TG-induced decay of [Ca2+]ER shown in (E) (post-TG t1/2) (J) were quantified for the time between 1,200 and 1,800 s.

Time points of ES and TG application are indicated with vertical lines in (A–D) (mock/ES; 1 μM TG). Mock denotes DMSO controls. Data are presented as means ± SEM. n.a., not analyzed; n.s., not significant; *p < 0.05; ***p < 0.001. N = 25–48 cells per experimental setting. See also Figure S2.