Akt depletion is an important determinant of L929 cell death following heat stress.
Exposure of mammalian cells to heat stress causes impairment of numerous physiological functions and activates a number of signaling pathways. Some of these pathways, such as induction of heat-shock proteins and activation of Akt, enhance the ability of cells to survive heat stress. On the other hand, heat stress can trigger cell-death signaling via activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/Jnk). Recently, it has been shown that kinases activated by heat stress can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate the activity of the cell death and survival pathways. We have found that Akt plays a central role in determining the fate of L929 fibroblast cells exposed to heat stress. In our experiments heat stress causes Akt depletion and L929 cells to undergo cell death. Heat-shock protein 70 (Hsp70) is known to prevent stress-induced cell death by interfering with the SAPK/Jnk signaling pathway. In our study, there is a very high level of induction of Hsp70, yet this is not sufficient to rescue Akt depletion and L929 from cell death. The Akt depletion is specific, since actin protein level does not change during the heat stress. Moreover, our studies show that L929 cells can recover from a short-term heat shock, whereby, Akt level is returned to normal following recovery from heat shock. Therefore, it appears that the fate of the prolonged heat-stressed fibroblast cells is determined by Akt level, and that return of Akt protein level to normal prevents cell death.
Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Sehamuddin
S
Galadari
Faisal
F
Thayyullathil
Abdulkader
A
Hago
Mahendra
M
Patel
Shahanas
S
Chathoth
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D004591:Electrophoresis, Polyacrylamide Gel; D018882:Heat Stress Disorders; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D051057:Proto-Oncogene Proteins c-akt