Expression of heat shock protein 27 in human renal cell carcinoma

Sarto, Cecilia; Valsecchi, Cristina; Magni, Fulvio; Tremolada, Lucia; Arizzi, Carmelo; Cordani, Nicoletta; Casellato, Stefano; Doro, Giancarlo; Favini, P.; Perego, R; Raimondo, Francesca; Ferrero, Stefano; Mocarelli, Paolo; Galli-Kienle, M.

doi:10.1002/pmic.200300797

Cited by 67 publications

(73 citation statements)

References 22 publications

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“…Previous 2D gel electrophoresis studies of heart tissues and cell lines reported largely diversified results for the number of HSP27 spots. Depending on the cell type, the number of isoforms with different phosphorylation status varied from 2 to 80 (10,42,44,47). Especially in pathogenic tissues, increased numbers of HSP27 spots have been observed in 2D gels, likely because of disintegration of HSP27 oligomers and also different degrees of phosphorylation, such as, for example, mono-, di-, and triphosphorylation.…”

Section: Attenuation Of Dox-induced Apoptosis In Heat-shocked Cardiacmentioning

confidence: 99%

Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27

Venkatakrishnan¹,

Tewari²,

Moldovan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27. Am J Physiol Heart Circ Physiol 291: H2680 -H2691, 2006. First published June 16, 2006 doi:10.1152/ajpheart.00395.2006 and its derivatives are used as chemotherapeutic drugs to treat cancer patients. However, production of DOX-mediated reactive oxygen species (ROS) by prolonged use of these drugs has been found to cause dilative cardiomyopathy and congestive heart failure. Thus various preventive modalities have been developed to avoid this side effect. We have found that the DOX-mediated oxidant-induced toxicity in cardiac cells could be minimized by hyperthermia-induced small heat shock protein 27 (HSP27); that is, this protein acts as an endogenous antioxidant against DOX-derived oxidants such as H 2O2. Heat shockinduced HSP27 was found to act as an antiapoptotic protein (reducing ROS and Bax-to-Bcl2 ratio) against DOX, and its phosphorylated isoforms stabilized F-actin remodeling in DOX-treated cardiac cells and, hence, attenuated the toxicity. Protein kinase assays and proteomic analyses suggested that higher expression of HSP27 and its phosphorylation are responsible for the protection in heat-shocked cells. Two-dimensional gel electrophoresis showed six isoforms (nonphosphorylated and phosphorylated) of HSP27. Matrix-assisted laser desorption/ionization time of flight analyses showed ␣-and ␤-isoforms of HSP27, which are phosphorylated by various protein kinases. Ser 15 and Ser 85 phosphorylation of HSP27 by MAPK-assisted protein kinase 2 was found to be the key mechanism in reduction of apoptosis and facilitation of F-actin remodeling. The present study illustrates that hyperthermia protects cells from DOX-induced death through induction and phosphorylation of HSP27 and its antiapoptotic and actin-remodeling activities. apoptosis; cardiomyopathy; hyperthermia ADRIAMYCIN DERIVATIVES, such as doxorubicin (DOX), are widely used as anticancer drugs. Unfortunately, prolonged use of these drugs to treat cancer patients has resulted in the development of dilative cardiomyopathy (DCM) and congestive heart failure (CHF) within a few years after cessation of treatment, irrespective of age and race (36). To avoid this side effect, new anthracyclin derivatives with less toxicity to the heart, new formulations in the form of encapsulation into delivery vehicles such as microemulsions, and new targeted delivery modalities to selectively deliver the drug to the desired site (preventing accumulation in the heart) have emerged (39).However, there has been no significant improvement in our ability to avoid this problem, and this effect has not been completely eliminated. At the same time, attempts to understand the actual mechanism of DOX-induced DCM and CHF have been appearing with increasing frequency in recent literature. Fortunately, the mechanisms whereby DOX and its analogs kill tumor cells (intended effect) and cause DCM and CHF (unwanted effects) are different, indicating...

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Section: Attenuation Of Dox-induced Apoptosis In Heat-shocked Cardiacmentioning

confidence: 99%

Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27

Venkatakrishnan¹,

Tewari²,

Moldovan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Previous studies have shown higher expression of HSP27 in ccRCC (27,(29)(30)(31)(32). We observed the same result.…”

Section: Discussionsupporting

confidence: 82%

Differencial proteome of clear-cell renal cell carcinoma (ccRCC) tissues

et al. 2013

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Purpose: We attempted to detect, for the first time in a Brazilian cohort, differences in protein expression between clear-cell renal cell carcinoma (ccRCC) and their normal adjacent tissues, aiming to identify biomarkers and/or therapeutic target candidates for this disease. Material and Methods: Twenty-four ccRCC and adjacent normal tissues were collected after surgery and their protein extracts were quantified, pooled and separated by two--dimensional polyacrylamide gel electrophoresis (2DE), followed by statistical analysis of the stained gels. Spots of interest were excised from the gels, digested with trypsin and identified by MALDI-TOF-TOF mass spectrometry. Results: Twenty-six differential spots were detected between the two classes of tissues, among which twenty were identified by mass spectrometry and sixteen were found to be non-redundant. Eleven proteins were either underexpressed or undetected in the ccRCC extracts, such as prohibitin and peroxiredoxin-3, whereas five were found to be overexpressed or exclusively detected in the ccRCC extract, including αβ crystalin and heat shock protein 27. Conclusions: Several proteins were detected at differential levels when compared to normal adjacent tissues, and, moreover, many have been previously described by their relationship with RCC. Therefore, this work corroborates previous reports on the search for biomarkers for ccRCC, as well as it points out new candidates that may be validated in future studies.

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“…The most acidic of the five isoforms of Hsp27 was detected almost exclusively in infected cells, indicating that PrV infection caused a sharp rise in these isoforms. Most probably, the charge variants are the result of differential phosphorylation, which was previously described for human (37,48) and bovine (28) Hsp27. A similar shift to higher phosphorylated forms of Hsp27 has been observed after treatment of bovine cells with cadmium (28), indicating that this reaction is not specific for infections with herpesviruses but rather reflects phosphorylation of Hsp27 during cellular stress (27).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Whole-Cell Proteome Analysis of Pseudorabies Virus-Infected Cells

Skiba

Mettenleiter

Karger

2008

J Virol

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A quantitative proteome study using the stable isotope labeling with amino acids in cell culture technique was performed on bovine kidney cells after infection with the alphaherpesvirus pseudorabies virus (PrV), the etiological agent of Aujeszky's disease. To enhance yields of proteins to be identified, raw extracts were fractionated by affinity solid-phase extraction with a combination of a cibacron blue F3G-A and a heparin matrix and with a phosphoprotein-specific matrix. After two-dimensional gel electrophoresis in different pH ranges between pH 3 and pH 10, 2,600 proteins representing 565 genes were identified by mass spectrometry and screened for virus-induced changes in relative protein levels. Four hours after infection, significant quantitative variations were found for constituents of the nuclear lamina, representatives of the heterogeneous nuclear ribonucleoproteins, proteins involved in membrane trafficking and intracellular transport, a ribosomal protein, and heat shock protein 27. Several proteins were present in multiple charge variants that were differentially affected by infection with PrV. As a common pattern for all these proteins, a mass shift in favor of the more acidic isoforms was observed, suggesting the involvement of viral or cellular kinases.Herpesviral genes are generally expressed in three kinetic classes (18,19), which are regulated sequentially by a number of positive and negative feedback mechanisms exerted by virusencoded proteins. However, herpesvirus infection also influences the expression of cellular genes, e.g., by host cell shutoff mechanisms that target the integrity of cellular mRNA and thus block the synthesis of cellular proteins. Herpes simplex virus type 1 (HSV-1), the prototypical alphaherpesvirus, expresses two shutoff proteins, ICP27 and pUL41. Whereas ICP27 interferes with mRNA splicing (16, 17), pUL41 degrades mRNA by virtue of its endoribonucleolytic activity (10, 29, 54), with specificity for mRNAs containing AU-rich elements (11). Homologs of both proteins are also present in pseudorabies virus (PrV), an alphaherpesvirus causing Aujeszky's disease. PrV, whose main host is the pig, infects numerous mammalian species except higher primates including humans. In contrast to HSV-1 ICP27, the PrV homolog pUL54 is dispensable for virus replication in cell culture (47,49). Transcript analyses of PrV-infected rat (44), human (6), and porcine (12) cells demonstrated alterations in the abundance of individual cellular transcripts, which resulted in the depletion or accumulation of specific mRNAs. Of the 9,850 genes examined in one study (6), the number of significantly up-or downregulated genes increased from approximately 1,000 to over 2,400 between 6 and 9 h after infection. Evaluation of the functions annotated for highly regulated cellular genes shows that PrV infection influences numerous cellular pathways and that genes involved in protein and nucleic acid metabolism, signaling, transport, cell cycle control, adhesion, transcription, the stress response, and innate ...

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Expression of heat shock protein 27 in human renal cell carcinoma

Cited by 67 publications

References 22 publications

Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27

Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27

Differencial proteome of clear-cell renal cell carcinoma (ccRCC) tissues

Quantitative Whole-Cell Proteome Analysis of Pseudorabies Virus-Infected Cells

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