In vivo heat-shock response in the brain: signalling pathway and transcription factor activation

Maroni, Paola; Bendinelli, Paola; Tiberio, Laura; Rovetta, Francesca; Piccoletti, Roberta; Schiaffonati, Luisa

doi:10.1016/j.molbrainres.2003.08.018

Cited by 53 publications

(34 citation statements)

References 69 publications

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“…These results suggest that mild heat shock can activate Rac1. It has been demonstrated that PI 3-kinase and PAK, signal molecules that are involved in the Rac1 signal pathway, are activated by heat shock (37,38), further supporting heat shock activation of Rac1. However, it is not clear how heat shock activates Rac1.…”

Section: Discussionmentioning

confidence: 93%

“…Thus, although Rac1 could produce ROS through activating NADPH oxidase (46), heat shock-induced JNK activation is likely regulated by the Rac1 signal pathway not involving ROS and NADPH oxidase. PAK, one of Rac1 downstream effectors and which is upstream of JNK, has been reported to be activated by heat shock (38). Therefore, the Rac1-PAK signal pathway may be responsible for heat shock-induced JNK activation.…”

Section: Discussionmentioning

confidence: 99%

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Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock

Han

Woo

et al. 2001

Journal of Biological Chemistry

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Heat shock induces c-Jun N-terminal kinase (JNK) activation as well as heat shock protein (HSP) expression through activation of the heat shock factor (HSF), but its signal pathway is not clearly understood. Since a small GTPase Rac1 has been suggested to participate in the cellular response to stresses, we examined whether Rac1 is involved in the heat shock response. Here we show that moderate heat shock (39 -41°C) induces membrane translocation of Rac1 and membrane ruffling in a Rac1-dependent manner. In addition, Rac1N17, a dominant negative mutant of Rac1, significantly inhibited JNK activation by heat shock. Since Rac1V12 was able to activate JNK, it is suggested that heat shock may activate JNK via Rac1. Similar inhibition by Rac1N17 of HSF activation in response to heat shock was observed. However, inhibitory effects of Rac1N17 on heat shockinduced JNK and HSF activation were reduced as the heat shock temperature increased. Rac1N17 also inhibited HSF activation by L-azetidine-2-carboxylic acid, a proline analog, and heavy metals (CdCl 2 ), suggesting that Rac1 may be linked to HSF activation by denaturation of polypeptides in response to various proteotoxic stresses. However, Rac1N17 did not prevent phosphorylation of HSF1 in response to these proteotoxic stresses. Interestingly, a constitutively active mutant Rac1V12 did not activate the HSF. Therefore, Rac1 activation may be necessary, but not sufficient, for heat shockinducible HSF activation and HSP expression, or otherwise a signal pathway(s) involving Rac1 may be indirectly involved in the HSF activation. In sum, we suggest that Rac1 may play a critical role(s) in several aspects of the heat shock response.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock

Han

Woo

et al. 2001

Journal of Biological Chemistry

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“…Heat shock proteins (HSP) are induced at hyperthermic temperatures, especially above 45ºC and HSPs can modify the induction of cell death [6]. Elevated levels of HSP are found when cells are subjected to elevated temperatures, drugs, UV irradiation, glucose deprivation, cytoskeletal perturbation, hypoxia or other stress [13][14][15][16][17][18][19][20][21]. Upregulation of HSPs protects cells and makes them more resistant to chemotherapy, hyperthermia and radiation treatments [6].…”

Section: Synergistic Effects Of Hyperthermia With Chemotherapymentioning

confidence: 99%

“…Upregulation of HSPs protects cells and makes them more resistant to chemotherapy, hyperthermia and radiation treatments [6]. HSP's are classified according to their molecular weights and help mediate cell damage by initiating mechanisms for repair of misfolded proteins that have been damaged or they can inhibit caspase activation and thus prevent apoptosis [18,[20][21][22]. HSPs 70, 90, and 27 can also promote cell survival mechanisms [13].…”

Section: Synergistic Effects Of Hyperthermia With Chemotherapymentioning

confidence: 99%

Clinical Relevance of Nanoparticle Induced Hyperthermia for Drug Delivery and Treatment of Abdominal Cancers

Levi‐Polyachenko¹

2011

TONMJ

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Abstract:The aim of this review is to introduce the reader to the potential clinical utility for the delivery of chemotherapy in the context of nanoparticles. We will present traditional methods of hyperthermia and then focus on the clinical technique for using intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination of colorectal cancer. Cellular mechanisms of hyperthermia as well as clinically effective chemotherapeutic agents are discussed. In the past decade carbon and metal nanoparticles have been explored for their ability to induce hyperthermia; however, many of these studies examine nanoparticles for tumor ablation at high temperatures. There are currently few studies that evaluate mild hyperthermia (below 43°C) generated by nanoparticles to enhance the delivery of chemotherapeutic agents. The fundamentals for generation of hyperthermia from carbon and metal nanoparticles is discussed as are the limitations and benefits of specific nanoparticles with chemotherapeutic agents. This review will show that there is significant potential for the use of nanoparticles to induce hyperthermia and increase the delivery of chemotherapeutic agents for treatment of colorectal cancer and other peritoneal disease.

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“…Some evidence suggests that the activation of Akt is enhanced immediately after heat stress [6,7] . Akt, a serine/ threonine kinase, plays a critical role in regulating neuronal cell survival responses.…”

Section: Introductionmentioning

confidence: 99%

Activation of PI3-K/Akt pathway for thermal preconditioning to protect cultured cerebellar granule neurons against low potassium-induced apoptosis

Cao

et al. 2007

Acta Pharmacologica Sinica

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Aim: This study was designed to investigate whether the activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is required for thermal preconditioning to protect rat cerebellar granule neurons (CGN) against apoptosis induced by low potassium, and to explore the possibility of a link between the upregulated heat shock protein (HSP)70 expression and Akt activation in the acquisition of neuroprotection induced by thermal preconditioning. Methods: CGN cultured for 8 d in vitro were switched to 5K medium for 24 h after thermal preconditioning (TP; 43.5 °C for 90 min, then 37 °C for 1 h). To study the role of the PI3-K/Akt pathway, a PI3-K inhibitor, LY294002 (20 µmol/L) was added into the cultures 1 h before TP. 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay and fluorescein diacetate staining were used to determine cell viability. Hoechst 33258 staining and agar gel electrophoresis were used to test the morphological and biological characters of CGN. Western blot analysis was employed to detect the levels of phospho-Akt, phospho-glycogen synthase kinase 3β (GSK3β) Akt, GSK3β, and HSP70. Results: TP protected CGN against apoptosis induced by low potassium. LY294002 inhibited the neuroprotective effect on CGN induced by TP. TP induced a robust activation of Akt and the inactivation of GSK3β via PI3-K. Furthermore, the activation of the PI3-K/Akt pathway by TP persisted for 24 h in the 5K cultures. LY294002 (20 µmol/L) failed to inhibit the upregulated HSP70 expression induced by TP. Conclusion: The activation of the PI3-K/Akt pathway is required for TP to protect CGN against apoptosis induced by low potassium, but the neuroprotective effect by Akt activation is not mediated through the downstream induction of HSP70 expression.

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In vivo heat-shock response in the brain: signalling pathway and transcription factor activation

Cited by 53 publications

References 69 publications

Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock

Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock

Clinical Relevance of Nanoparticle Induced Hyperthermia for Drug Delivery and Treatment of Abdominal Cancers

Activation of PI3-K/Akt pathway for thermal preconditioning to protect cultured cerebellar granule neurons against low potassium-induced apoptosis

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