Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells

Leal, Rodrigo Bainy; Posser, Thaís; Rigon, Ana Paula; Oliveira, Claudio; Gonçalves, Carlos Alberto; Gelain, Daniel Pens; Dunkley, Peter R.

doi:10.1016/j.tox.2007.01.023

Cited by 27 publications

(17 citation statements)

References 65 publications

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“…As shown in Table 2 and Figure 2B, our study revealed increases of phosphorylated ERK and JNK in all the transformants (JB6P+/UVB, 1.5‐ and 1.9‐fold; JB6P+/H 2 O 2 , 2.2‐ and 1.5‐fold; JB6P+/Cd, 1.9‐ and 1.5‐fold respectively) as compared to JB6P+ cells (1.2‐ and 0.9‐fold respectively, levels in JB6P− standardized as 1.0). These findings coincided and supported other observations, which have suggested the critical involvement of MAPK in tumor promotion and carcinogenesis 18, 41, 42. Notably, no significant alterations of p38 activities were observed (data not shown); these results are in contrast to the reports indicating the involvement of p38 after UV exposure 43, 44.…”

Section: Resultssupporting

confidence: 91%

Common and distinct mechanisms of different redox‐active carcinogens involved in the transformation of mouse JB6P+ cells

Yang

Misner

Chiu

et al. 2007

Molecular Carcinogenesis

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We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H2O2 or CdCl2. Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (∼six folds) in soft agar as compared to their JB6P+ parent cells and were associated with increased intracellular reactive oxygen species (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors that are rapidly activated by elevated intracellular ROS levels, and their composition is important in the process of cellular transformation and/or tumor progression. To investigate if carcinogenesis induced by distinct carcinogens was via similar molecular mechanisms in these transformants, gel mobility shift and immunoblot analyses were utilized to determine the distinct AP-1 compositions. Compared to parent JB6P+ cells, the gain of JunB and Fra-1 in AP-1 DNA binding complexes was markedly increased in all transformed cells, which might contribute to a more proliferative phenotype, while loss of Fra-2 occurred in JB6P+/H2O2 and JB6P+/Cd cells. Differential AP-1 components in the transformants suggested that their transformations might be mediated by distinct transcription signalings with distinct AP-1 dimer compositions. However, all three transformants exhibited increased activation of pathways involved in cell proliferation (ERK/Fra-1/AP-1 and JNK/c-jun/AP-1) and anti-apoptosis (Bcl-xl). The development of the JB6P+ transformants (JB6P+/UVB; JB6P+/H2O2; JB6P+/Cd) provides a unique tool to study the mechanisms that contribute to different redox-active carcinogens in a single model.

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Section: Resultssupporting

confidence: 91%

Common and distinct mechanisms of different redox‐active carcinogens involved in the transformation of mouse JB6P+ cells

Yang

Misner

Chiu

et al. 2007

Molecular Carcinogenesis

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“…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). However, other stress-related proteins that were identified and quantified showed no significant changes in relative protein levels (data not shown).…”

Section: Discussionmentioning

confidence: 58%

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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“…Occasionally, cells that express readily detectable levels of Hsp27 are refractory to further induction of this sHSP by Cd, as has been shown for astroglia cells (Opanashuk and Finkelstein 1995). In a number of studies, Cd induced a robust and swift phosphorylation of Hsp27 in various cell types, including macrophages, renal podocytes, renal mesangial cells, and adrenal chromaffin cells (Radloff et al 1998;Eichler et al 2005;Hirano et al 2005;Leal et al 2007). In these cells, Cd is likely to activate signaling pathways that do not involve the ER.…”

Section: Discussionmentioning

confidence: 93%

“…With respect to Hsp27, this outcome was not expected because Cd robustly induced phosphorylation of this sHSP in a number of cell types (Radloff et al 1998;Eichler et al 2005;Hirano et al 2005;Leal et al 2007). In those studies, however, cells were exposed to Cd for shorter time periods (typically 0.5-2 hours) compared with the experiments shown in Figure 1A,B.…”

Section: Induction Of Hsp22mentioning

confidence: 87%

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Induction of Hsp22 (HspB8) by estrogen and the metalloestrogen cadmium in estrogen receptor– positive breast cancer cells

et al. 2007

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Estrogen (E 2 ) plays a critical role in the etiology and progression of human breast cancer. The estrogenic response is complex and not completely understood, including in terms of the involved responsive genes. Here we show that Hsp22 (synonyms: HspB8, E2IG1, H11), a member of the small heat shock protein (sHSP) superfamily, was induced by E 2 in estrogen receptor-positive MCF-7 breast cancer cells, resulting in an elevated Hsp22 protein level, whereas it was not induced in estrogen receptor-negative MDA-MB-231 cells. This induction was prevented by the pure anti-estrogen ICI182780 (faslodex, fulvestrant), whereas tamoxifen, a substance with mixed estrogenic and antiestrogenic properties, had no major inhibitory effect on this induction, nor did it induce Hsp22 on its own. Cadmium (Cd) is an environmental pollutant with estrogenic properties (metalloestrogen) that has been implicated in breast cancer. Treatment of MCF-7 cells with Cd also resulted in induction of Hsp22, and this induction was also inhibited by ICI182780. In live MCF-7 cells, Hsp22 interacted at the level of dimers with Hsp27, a related sHSP, as was shown by quantitative fluorescence resonance energy transfer measurements. In cytosolic extracts of MCF-7 cells, most of the E 2 -and Cd-induced Hsp22 was incorporated into high-molecular mass complexes. In part, Hsp22 and Hsp27 were components of distinct populations of these complexes. Finally, candidate elements in the Hsp22 promoter were identified by sequence analysis that could account for the induction of Hsp22 by E 2 and Cd. Taken together, Hsp22 induction represents a new aspect of the estrogenic response with potential significance for the biology of estrogen receptorpositive breast cancer cells.

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Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells

Cited by 27 publications

References 65 publications

Common and distinct mechanisms of different redox‐active carcinogens involved in the transformation of mouse JB6P+ cells

Common and distinct mechanisms of different redox‐active carcinogens involved in the transformation of mouse JB6P+ cells

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

Induction of Hsp22 (HspB8) by estrogen and the metalloestrogen cadmium in estrogen receptor– positive breast cancer cells

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