Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis

Rappa, Francesca; Unti, Elettra; Baiamonte, P.; Cappello, Francesco; Scibetta, Nunzia

doi:10.4081/ejh.2013.e20

Cited by 31 publications

(25 citation statements)

References 24 publications

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“…It has been found to be accumulated in the cytoplasm during apoptotic activation [ 55 ]. In contrast, HSP60 levels were reported to be significantly higher in cytoplasm of neuroepithelial tumors [ 56 ]. This chaperone has also been considered as a potential antitumor target [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

HSP60 plays a regulatory role in IL-1β-induced microglial inflammation via TLR4-p38 MAPK axis

Swaroop

Sengupta

Suryawanshi

et al. 2016

J Neuroinflammation

101

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BackgroundIL-1β, also known as “the master regulator of inflammation”, is a potent pro-inflammatory cytokine secreted by activated microglia in response to pathogenic invasions or neurodegeneration. It initiates a vicious cycle of inflammation and orchestrates various molecular mechanisms involved in neuroinflammation. The role of IL-1β has been extensively studied in neurodegenerative disorders; however, molecular mechanisms underlying inflammation induced by IL-1β are still poorly understood. The objective of our study is the comprehensive identification of molecular circuitry involved in IL-1β-induced inflammation in microglia through protein profiling.MethodsTo achieve our aim, we performed the proteomic analysis of N9 microglial cells with and without IL-1β treatment at different time points. Expression of HSP60 in response to IL-1β administration was checked by quantitative real-time PCR, immunoblotting, and immunofluorescence. Interaction of HSP60 with TLR4 was determined by co-immunoprecipitation. Inhibition of TLR4 was done using TLR4 inhibitor to reveal its effect on IL-1β-induced inflammation. Further, effect of HSP60 knockdown and overexpression were assessed on the inflammation in microglia. Specific MAPK inhibitors were used to reveal the downstream MAPK exclusively involved in HSP60-induced inflammation in microglia.ResultsTotal 21 proteins were found to be differentially expressed in response to IL-1β treatment in N9 microglial cells. In silico analysis of these proteins revealed unfolded protein response as one of the most significant molecular functions, and HSP60 turned out to be a key hub molecule. IL-1β induced the expression as well as secretion of HSP60 in extracellular milieu during inflammation of N9 cells. Secreted HSP60 binds to TLR4 and inhibition of TLR4 suppressed IL-1β-induced inflammation to a significant extent. Our knockdown and overexpression studies demonstrated that HSP60 increases the phosphorylation of ERK, JNK, and p38 MAPKs in N9 cells during inflammation. Specific inhibition of p38 by inhibitors suppressed HSP60-induced inflammation, thus pointed towards the major role of p38 MAPK rather than ERK1/2 and JNK in HSP60-induced inflammation. Furthermore, silencing of upstream modulator of p38, i.e., MEK3/6 also reduced HSP60-induced inflammation.ConclusionsIL-1β induces expression of HSP60 in N9 microglial cells that further augments inflammation via TLR4-p38 MAPK axis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0486-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

HSP60 plays a regulatory role in IL-1β-induced microglial inflammation via TLR4-p38 MAPK axis

Swaroop

Sengupta

Suryawanshi

et al. 2016

J Neuroinflammation

101

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“…As such, the chaperonin has become the subject of studies aiming at determining its precise role as etiologic-pathogenic factor and also aiming at inventing new diagnostic and therapeutic ways centered on it. Adrenal gland Adrenal Cushing's tumor [168] Bladder Transitional cell carcinoma; carcinosarcoma [169][170][171] Bone marrow, blood, lymph nodes Acute myeloid leukemia; Hodgkin's lymphoma [155,[172][173][174] Brain Astroglyoma; glioblastoma; meningioma [175][176][177][178][179] Breast Breast ductal carcinoma [180,181] Esophagus Oesophageal carcinoma [182,183] Large bowel Adenocarcinoma [23,169,[184][185][186][187] Liver Hepatocellular carcinoma [188] Lung Bronchial carcinoma [25,26,189,190] Ovary Serous ovarian cancer [191] Prostate Prostate carcinoma [24,[192][193][194] Stomach Gastric maltoma [195] Uterus Exocervical carcinoma [22,196] Adapted from [2]. ATP synthase [197] Dihydrofolatereductase [37,46] Hsp10 [37,41] Human Carbonicanhydrase II [37,198,…”

Section: Expert Opinionmentioning

confidence: 99%

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

Cappello

Gammazza

Piccionello

et al. 2013

Expert Opinion on Therapeutic Targets

140

133

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“…The HSP60 secretion is linked to widespread intercellular communication events with various biologic effects. In brain tumors, HSP60 is overexpressed [68,69], and its secretion may be a mechanism involved in cell transformation and in tumor progression, suggesting that HSP60 is a potential therapeutic target for brain tumors treatment [42].…”

Section: Discussionmentioning

confidence: 99%

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Bavisotto

Gammazza

Cascio

et al. 2020

IJMS

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The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial–mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 µM of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 µM. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 µM of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin.

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Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis

Cited by 31 publications

References 24 publications

HSP60 plays a regulatory role in IL-1β-induced microglial inflammation via TLR4-p38 MAPK axis

HSP60 plays a regulatory role in IL-1β-induced microglial inflammation via TLR4-p38 MAPK axis

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

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