Distribution of HSP70, protein kinase C, and spectrin is altered in lymphocytes during a fever-like hyperthermia exposure.
Many B and T lymphocytes display a significant heterogeneity with respect to the subcellular distribution of the cytoskeletal protein spectrin and protein kinase C (PKC), both of which often can be found in a large cytoplasmic aggregate in these cell types. In addition to spectrin and PKC, we recently have reported that HSP70 is also a component of this lymphocyte aggregate. Moreover, these three proteins can undergo dynamic and reversible changes in their localization causing "assembly" of the aggregate in response to various conditions associated with lymphocyte activation, indicating that this naturally occurring aggregate structure is sensitive to activation status. We show here that the same changes in HSP70/spectrin/PKC localization induced by PKC activation also can be caused, in vitro and in vivo, by a mild hyperthermia exposure, as occurs during a natural fever (39.5-40 degrees C, 2-12 hr). This mild heat exposure also triggers the activation of PKC, a major heat shock response, and lymphocyte proliferation. The increase in PKC activity, HSP70-spectrin-PKC aggregate formation, and heat shock protein expression resulting from exposure to fever-like hyperthermia are all inhibited by calphostin C, a specific inhibitor of PKC. These data demonstrate that changes observed during lymphocyte activation could be induced by a mild hyperthermia exposure occurring during a normal febrile episode.
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Department of Molecular and Cellular Biology, Roswell Cancer Institute, Buffalo, New York, USA.
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D000818:Animals; D002451:Cell Compartmentation; D005260:Female; D005334:Fever / Q000503:physiopathology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013049:Spectrin / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D013049:Spectrin; D011493:Protein Kinase C