Discordant activation of stress-activated protein kinases or c-Jun NH2-terminal protein kinases in tissues of heat-stressed mice.
Stress-activated protein kinases (SAPK) or c-Jun NH2-terminal protein kinases (JNK) are believed to be crucial signal transducers between stress stimuli and genetic responses in mammalian cells. These kinases are activated in various types of in vitro cultured cells by heat shock, but a similar activation of SAPK/JNK in tissues in vivo has yet to be shown. In the present study, C57BL/6 mice were exposed to elevated ambient temperature for various time periods, and SAPK/JNK activities determined in protein extracts of brain, heart, liver, spleen, lung, and kidney using protein kinase assay and Western blot analyses. The time course and relative magnitude of the heat-induced SAPK/JNK activity differed among tissues of the same animal. Significant activation of SAPK/JNK was achieved in heart, liver, and kidney at 60 or 90 min of heat stress. This increased activity of SAPK/JNK kinases was demonstrated to result from activation or phosphorylation of existing proteins in tissues. The maximal activation of these kinases showed no direct relationship with the elevation in body temperature (38-40.5 degrees C). Interestingly, SAPK/JNK activation did not occur in lung, brain, or spleen of the same heat-stressed mouse. Although elevated body temperature (40.5 degrees C) did not result in SAPK/JNK activation in spleen and lung tissues, heat stress induced SAPK/JNK activation in cultured organs or fibroblasts derived from spleen or lung of C57BL/6 mice. Furthermore, activity and amount of SAPK/JNK proteins were the most abundant in brain among tissues examined. Thus, our findings demonstrated that heat shock-induced SAPK/JNK activation in vivo lacks much of the characteristic coordinate control of activation of cultured cell lines, and suggests that the mechanisms controlling SAPK/JNK activation are influenced by physiologic factors that cannot be studied in vitro.
Hu
Y
Y
Institute for Biomedical Aging Research, Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
Metzler
B
B
Xu
Q
Q
D000818:Animals; D001921:Brain / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D006358:Hot Temperature; D048031:JNK Mitogen-Activated Protein Kinases; D008168:Lung / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011487:Protein Conformation; D013312:Stress, Physiological / Q000201:enzymology*
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases