Heat shock (HS) activates mitogen-activated protein (MAP) kinases. Although prior exposure to nonlethal HS makes cells refractory to the lethal effect of a subsequent HS, it is unclear whether this also occurs in MAP kinase activation. This study was undertaken to evaluate the effect of a heat pretreatment on MAP kinase activation by a subsequent HS and to elucidate its possible mechanism. Preheating did not make BEAS-2B cells refractory to extracellular signal-regulated protein kinase ( The mitogen-activated protein (MAP) 1 kinase cascade is an intracellular signaling module ubiquitous among eukaryotes.It is one of the most ancient and evolutionarily conserved signaling pathways from unicellular organisms like brewers' yeast to complex organisms such as humans (1). Three major groups of MAP kinases are found in mammalian cells: extracellular signal-regulated protein kinase (ERK) (2), p38 MAP kinase (3), and c-Jun N-terminal kinase (JNK) (4 -6). MAP kinases regulate many cellular activities, which range from gene expression to mitosis, movement, metabolism, and apoptosis. These MAP kinases are activated by the dual phosphorylations of neighboring threonine and tyrosine residues in response to various extracellular stimuli (7,8).Heat shock (HS) induces two major signaling events, the transcriptional induction of heat shock proteins (HSPs) (9 -11) and the activation of MAP kinases (12)(13)(14). HSPs are a group of proteins that range in molecular mass from 8 to 110 kDa and appear to confer protection against a wide range of cellular and tissue injuries. As molecular chaperones, HSPs have the capacity to bind to folded intermediates and misfolded or denatured proteins and prevent their irreversible denaturation. Furthermore, HSPs assist in the renaturation and correct refolding of misfolded proteins (15-17). Moreover, cells were found to acquire transient resistance to the lethal effect of exposure to HS by prior exposure to a nonlethal HS (18, 19), a phenomenon termed thermotolerance, and the overexpression of HSP was found to confer resistance against thermal injury and to increase cell survival (20 -23). This suggests that HSPs have a role in the acquisition of thermotolerance. However, it is unclear whether preheated cells are refractory to MAP kinase activation by a subsequent HS; very little is known about the mechanisms involved.In this study, we found that preheating did not make cells refractory to ERK and JNK activation by a second HS but rather that it accelerated their inactivation. Moreover, this rapid inactivation was dependent on de novo protein synthesis. HS increased MAP kinase phosphatase-1 (MKP-1) expression, and its phosphorylated form (p-MKP-1) was found to be associated with this rapid ERK and JNK inactivation. MKP-1 phosphorylation and the rapid inactivation of ERK were inhibited by blocking HSP70 induction in preheated cells. These results support the conclusion that preheating accelerated MAP kinase inactivation after a subsequent heat treatment and that this accelerated inactivation is rel...

No abstract

No abstract

No abstract