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. 2022 Jan 18;132(2):e149711. doi: 10.1172/JCI149711

Figure 9. Adenine and specific purine ribonucleosides are myocyte-derived proapoptotic molecules that in combination cause cell death of nonmyocytes.

Figure 9

(A) Schematic shows ENPP1+ATP MCndM pass through the C18 HPLC column. Effects of eluted fractions of ENPP1+ATM MCndM on cell death (arrowheads) of CFs. Scale bar: 50 μm. (B) Effect of 7 metabolites on cell death (filled arrowheads) of CFs and its rescue (unfilled arrowheads) by uridine and (C) quantitation of cell death (n = 9). Scale bar: 50 μm. (D) CFs treated with 7 compounds together and following subtraction of each one from the combined solution show absence of cell death (unfilled arrowheads) when adenine is removed. Cell death, filled arrowheads. Scale bar: 50 μm. (E) Quantitation of cell death (n = 4). (F) Effects of cell death (filled arrowheads) following addition of adenine alone or adenine combined with specific purine nucleosides or orotate and (G) quantitation of cell death (n = 3). Scale bar: 50 μm. (H) Effect of OMP or uridine in rescuing cell death following addition of adenine and adenosine to CFs (filled and unfilled arrowheads) and (I) quantitation of cell death (n = 6). Scale bar: 50 μm. (J) CFs overexpressing yeast adenine deaminase treated with vehicle MCndM or ENPP1+ATP MCndM showing decreased cell death of CFs overexpressing adenine deaminase (filled and unfilled arrowheads). (K) Quantitation of cell death (n = 3). Scale bar: 50 μm. Data are represented as mean ± SEM. **P < 0.01; *P < 0.05, 2-tailed Student’s t test (K) or ordinary 1-way ANOVA with Tukey’s multiple comparison test (C, E, G, and I).