Table 3.
Effect of calpain inhibitor PD150606 (100 μM) on poststress TMRM fluorescence and survival
| TMRM Fluorescence 5 h post-stress, % no-stress control | |
|---|---|
| Stress alone | Stress + PD150606 pretreat |
| 12.5 ± 1.8 (12) | 24.9 ± 2.6* (12) |
| Cell survival, % | ||
|---|---|---|
| Stress alone | Stress + PD150606 pretreat | Stress + PD150606 stress onset |
| 26 ± 3 | 50 ± 3* | 52.5 ± 4* |
Values are means ± SE, with number of culture wells shown in parentheses. Pretreat indicates that PD150606 was present 2 h before, during, and after the stress; stress onset indicates drug presence during and after the stress. TMRM fluorescence was measured 5 h post-stress (high-[K+] medium throughout). Cell survival was measured 24 h post-stress (live/dead assay, see materials and methods).
P < 0.001 compared with cultures stressed without drug. The protection afforded by PD150606 did not extend to 48 h post-stress, when survival measured in both PD150606-treated and nontreated cultures was similar (18-21%), a result repeated in 2 additional experiments. Long-term exposure to this drug may itself be toxic, because in nonheated cultures a 48-h exposure to PD150606 reduced survival from 90 to 39.5% as measured by propidium iodide exclusion.