Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response

Abstract

SUMMARYIn the present study we investigated the signal transduction cascades triggered by acute thermal stress in Mytilus galloprovincialis gills. This particular species has been reported to exhibit a significant tolerance to high temperatures; thus, it was intriguing to examine the molecular mechanisms responsible for this extraordinary trait. In particular, exposure to 30°C was found to cause a significant and sustained stimulation of p38-MAPK phosphorylation while the activation profile of JNKs was transient and relatively moderate. We also observed that hyperthermia induced apoptosis as a delayed response, with both MAPK subfamilies rapidly translocating to the nucleus. The phosphorylation of cJun, ATF2 and NFB was detected next. Using selective inhibitors, phosphorylation of these transcription factors was established to be dependent on p38-MAPK or JNKs. Subsequently, potential changes in gene expression were assessed. In this context, hyperthermia resulted in the transcriptional upregulation of Hsp70 and MT20 genes with a widely known salutary effect, preserving mussel fitness and performance under adverse environmental conditions. Interestingly, p38-MAPK and JNKs were found to mediate the hyperthermia-induced Hsp70 and MT20 upregulation as well as the delayed induction of apoptosis under the interventions studied. Overall this is, to our knowledge, the first time that an insight into the compensatory survival 'programme' initiated in Mytilus galloprovincialis gills, contributing to this organism's exceptional tolerance to thermal stress, has been gained. In particular, we provide evidence demonstrating the principal role of p38-MAPK and JNKs in transducing the stress signal via mobilization of specific transcription factors and the transcriptional upregulation of cytoprotective genes.

The impact of acute temperature stress on hemocytes of invasive and native mussels (Mytilus galloprovincialisandM. californianus): DNA damage, membrane integrity, apoptosis and signalling pathways

“…Our results showed that phospho-p38-MAPK levels increased significantly in hemocytes of M. galloprovincialis at 28°C; however, there was no significant change in hemocytes of M. californianus under this condition. Similarly, exposure to high temperature was found to cause a significant and sustained stimulation of p38-MAPK phosphorylation in the gill tissue of M. galloprovincialis (Gourgou et al, 2010;Kefaloyianni et al, 2005). Our results indicate that M. californianus might lose this component of the cellular stress response at temperatures of 28°C and higher, whereas M. galloprovincialis retains this ability.…”

“…Gill tissue of M. galloprovincialis (Gourgou et al, 2010) and mantle tissue and posterior adductor muscle of both M. galloprovincialis and M. barbatus also showed activation of JNK at high temperature (Anestis et al, 2007;Anestis et al, 2008), suggesting a common cellular stress response to heat stress in different cell types of these two mussels. The results of the present study showed that both cold and heat stress induced a significant increase in JNK phosphorylation in hemocytes of M. galloprovincialis, with the strongest expression at 28°C.…”

“…Recently, studies have demonstrated that p38-MAPK and JNK play crucial roles in the adaptive responses to thermal, osmotic, oxidative and heavy metal stresses in mussels (Kefaloyianni et al, 2005;Gaitanaki et al, 2007;Evans and Somero, 2010;Gourgou et al, 2010). For example, hyperthermia (30°C), hypothermia (4°C) and heavy metals induced a significant activation of p38-MAPK in gill and mantle tissue of M. galloprovincialis (Kefaloyianni et al, 2005).…”

“…It was demonstrated that p38-MAPK and JNK activity showed a close relationship with blockage of apoptosis after thermal stress in mammalian cells lines (Brown and Benchimol, 2006;Murai et al, 2010). Although much less is known about these responses in non-model species, p38-MAPK and JNK activation were shown to be induced by thermal stress in gill, mantle tissue or posterior adductor muscle of M. galloprovincialis or the bearded horse mussel Modiolus barbatus (Kefaloyianni et al, 2005;Anestis et al, 2007;Anestis et al, 2008;Gourgou et al, 2010).…”

Thermotherapy-induced reduction in glioma invasiveness is mediated by tumor necrosis factor-alpha

“…A new method to treat malignant glioma by thermotherapy has been used for patients with malignant glioma (Du et al, 2009). Thermotherapy is a comprehensive treatment that is gradually being recognized by clinicians; it has a characteristically precise role and has no known side effects (Iwasaki et al, 1993;Ivarsson et al, 2003;Gourgou et al, 2010;James et al, 2010). Increasing evidence suggests that there is an evident decrease in both tumor surgical relapse rate and mortality following thermotherapy treatment (Jurivich et al, 1995).…”