| First Author | Nagarsekar A | Year | 2012 |
| Journal | Am J Respir Cell Mol Biol | Volume | 47 |
| Issue | 6 | Pages | 824-33 |
| PubMed ID | 22962066 | Mgi Jnum | J:204044 |
| Mgi Id | MGI:5529440 | Doi | 10.1165/rcmb.2012-0105OC |
| Citation | Nagarsekar A, et al. (2012) Hyperthermia promotes and prevents respiratory epithelial apoptosis through distinct mechanisms. Am J Respir Cell Mol Biol 47(6):824-33 |
| abstractText | Hyperthermia has been shown to confer cytoprotection and to augment apoptosis in different experimental models. We analyzed the mechanisms of both effects in the same mouse lung epithelial (MLE) cell line (MLE15). Exposing MLE15 cells to heat shock (HS; 42 degrees C, 2 h) or febrile-range hyperthermia (39.5 degrees C) concurrent with activation of the death receptors, TNF receptor 1 or Fas, greatly accelerated apoptosis, which was detectable within 30 minutes and was associated with accelerated activation of caspase-2, -8, and -10, and the proapoptotic protein, Bcl2-interacting domain (Bid). Caspase-3 activation and cell death were partially blocked by inhibitors targeting all three initiator caspases. Cells expressing the IkappaB superrepessor were more susceptible than wild-type cells to TNF-alpha-induced apoptosis at 37 degrees C, but HS and febrile-range hyperthermia still increased apoptosis in these cells. Delaying HS for 3 hours after TNF-alpha treatment abrogated its proapoptotic effect in wild-type cells, but not in IkappaB superrepressor-expression cells, suggesting that TNF-alpha stimulates delayed resistance to the proapoptotic effects of HS through an NF-kappaB-dependent mechanism. Pre-exposure to 2-hour HS beginning 6 to16 hours before TNF-alpha treatment or Fas activation reduced apoptosis in MLE15 cells. The antiapoptotic effects of HS pretreatment were reduced in TNF-alpha-treated embryonic fibroblasts from heat shock factor-1 (HSF1)-deficient mice, but the proapoptotic effects of concurrent HS were preserved. Thus, depending on the temperature and timing relative to death receptor activation, hyperthermia can exert pro- and antiapoptotic effects through distinct mechanisms. |
