Cytosolic thioredoxin peroxidase I is essential for the antioxidant defense of yeast with dysfunctional mitochondria

The specific role of cytosolic thioredoxin peroxidase I (cTPx I), encoded by TSA1 (thiol-speciric antioxidant), was investigated in the oxidative stress response of Saccharomyces ceravisiae. In most cases, deletion of TSA1 has showed only a slight effect on hydrogen peroxide sensitivity. However, when the functional state of the mitochondria was compromised, the necessity of TSA1 in cell protection against this oxidant was much more evident. All the procedures used to disrupt the mitochondrial respiratory chain promoted increases in the generation of H2O2 in Cells, which could be related to their elevated sensitivity to oxidative stress. In. fact, TSA1 is highly expressed when cells with respiratory deficiency are exposed to H2O2. In conclusion, our results indicate that cTPx I is a key component of the antioxidant defense in respiratory-deficient cells. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.509343043

Yeast oxidative stress response - Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state

We investigated the changes in the oxidative stress response of yeast cells suffering mitochondrial dysfunction that could impair their viability. First, we demonstrated that cells with this dysfunction rely exclusively on cytosolic thioredoxin peroxidase I (cTPxI) and its reductant sulfiredoxin, among other antioxidant enzymes tested, to protect them against H2O2-induced death. This cTPxI-dependent protection could be related to its dual functions, as peroxidase and as molecular chaperone, suggested by mixtures of low and high molecular weight oligomeric structures of cTPxI observed in cells challenged with H2O2. We found that cTPxI deficiency leads to increased basal sulfhydryl levels and transcriptional activation of most of the H2O2-responsive genes, interpreted as an attempt by the cells to improve their antioxidant defense. On the other hand, mitochondrial dysfunction, specifically the electron transport blockage, provoked a huge depletion of sulfhydryl groups after H2O2 treatment and reduced the H2O2-mediated activation of some genes otherwise observed, impairing cell defense and viability. The transcription factors Yap1 and Skn7 are crucial for the antioxidant response of cells under inhibited electron flow condition and probably act in the same pathway of cTPxI to protect cells affected by this disorder. Yap1 cellular distribution was not affected by cTpxI deficiency and by mitochondrial dysfunction, in spite of the observed expression alterations of several Yap1-target genes, indicating alternative mechanisms of Yap1 activation/deactivation. Therefore, we propose that cTPxI is specifically important in the protection of yeast with mitochondrial dysfunction due to its functional versatility as an antioxidant, chaperone and modulator of gene expression.273480581

Peroxiredoxin I, platelet-derived growth factor A, and platelet-derived growth factor receptor alpha are overexpressed in carcinoma ex pleomorphic adenoma: association with malignant transformation

Carcinoma ex pleomorphic adenoma is a rare salivary gland malignancy. It constitutes an important model for the study of carcinogenesis, as it can display the tumor in different stages of progression, from benign pleomorphic adenoma to frankly invasive carcinoma. Growth signaling pathways undergo continuous activation in human tumors, commonly as a consequence of the overexpression of ligands and receptors such as platelet-derived growth factor and platelet-derived growth factor receptor. Hydrogen peroxide is produced after platelet-derived growth factor receptor activation, and it is essential for the sequential phosphorylation cascade that drives cell proliferation and migration. By their ability to degrade hydrogen peroxide, peroxiredoxins are involved in growth factor signaling regulation and in the oxidative stress response. To verify the potential association of peroxiredoxin 1, platelet-derived growth factor-A, and platelet-derived growth factor receptor-a with carcinoma ex pleomorphic adenoma progression, we investigated the expression of these molecules in carcinoma ex pleomorphic adenoma showing different degrees of invasion. The peroxiredoxin 1, platelet-derived growth factor-A, and platelet-derived growth factor receptor-a proteins were present in remnant pleomorphic adenoma to only a small extent, but, collectively, they were highly expressed as soon as the malignant phenotype was achieved and remained at elevated concentrations during progression to the advanced stages of carcinoma ex pleomorphic adenoma. In addition, their locations overlapped significantly, strengthening their connection to this growth-signaling pathway. Our results indicate that carcinoma ex pleomorphic adenoma cells acquire at least 2 significant advantages relative to their normal counterparts: resistance to oxidative stress-induced apoptosis, conferred by high peroxiredoxin I concentrations, and sustained growth, reflecting platelet-derived growth factor-A and platelet-derived growth factor receptor-a overexpression. (c) 2009 Elsevier Inc. All rights reserved.40339039

Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Oncocytic lesions, particularly frequent in the salivary glands, are characterized by cells with an atypical accumulation of mitochondria. This accumulation has been recognized as a compensatory mechanism to intrinsic functional defects of these organelles, resulting in energy production impairment and increased generation of reactive oxygen species (ROS), including hydrogen peroxide (H(2)O(2)). Peroxiredoxin I (Prx I) is a H(2)O(2) scavenging protein and the expression of its yeast homolog was reported to be influenced by mitochondrial function. Methods: In this study, we evaluated Prx I expression in oncocytic lesions of salivary glands by immunohistochemistry. Results: Our results showed that Prx I is overexpressed in oncocytes regardless of the salivary gland lesion where they appear. Conclusions: These results suggest that Prx I expression in oncocytes is related to its ability to decompose mitochondrial-derived H(2)O(2) and that it could provide to the cells a protective role in an environment that, by continuously producing potential DNA-damaging ROS, predisposes to genome instability and cellular transformation.386514517Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

FGF-2 is overexpressed in myoepithelial cells of carcinoma ex-pleomorphic adenoma in situ structures

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Increasing emphasis has been placed on the role of myoepithelial cells, the contractile components of secretory glands, in the in situ to invasive carcinoma transition. These cells are placed at the interface between luminal epithelial cells and the stromal compartment, which favors their crosstalk with all other cell types comprising the tumor micro-environment. To obtain some clues about this cross-talk and also to better understand our previous immunoprofile study of myoepithelial cells in salivary gland carcinoma ex-pleomorphic adenoma (CXPA), we investigated FGF-2 expression in CXPA in situ structures as well as in cells cultured under conditions attempting to simulate the cellular interactions of this tumor stage. We have observed by immunohistochemistry that myoepithelial cells of CXPA in situ structures over-express FGF-2. In addition, our results supported by qPCR and Western blotting, demonstrated that the expression of FGF-2 in the benign myoepithelial cells was in fact increased by stimulation with the conditioned medium from malignant cells. Low molecular weight FGF-2, known to be primarily released from the cells to exert its biological activity through receptors, was the predominant FGF-2 form detected in the benign myoepithelial cells. Specific FGF-2 receptors were found in the malignant epithelial but not in the benign myoepithelial cells of CXPA, indicating a paracrine role for benign myoepithelial cell-derived FGF-2. Abnormal paracrine myoepithelial/epithelial cell interactions and also myoepithelial/stromal cell interactions could favor tumor growth, invasion and metastasis.O TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE FEVEREIRO DE 2015.241155160Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [04/07960-0, 08/58721-7, 08/58722-3

Intravascular papillary endothelial hyperplasia: report of 2 cases and immunohistochemical study

Intravascular papillary endothelial hyperplasia (IPEH) is a benign, nonneoplastic, vascular lesion. The main significance of the lesion lies in the fact that it may be mistaken for angiosarcoma. Oral lesions are uncommon and the present paper reports 2 cases of oral IPEH, in different sites. Histologically, the tissue was characterized by papillary fronds lined by proliferating endothelium. Immunohistochemically (IHC), the lesion was positive for CD34, smooth muscle actin (SMA), type I and IV collagen, vimentin, and laminin, but it was negative for CD105. Local excision was the treatment of choice. No recurrence was observed during a 1-year and 6-month follow-up period, respectively. The clinical, histological, and immunohistochemical characteristics are discussed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: 708-11)106570871

Angiogenesis in salivary carcinomas with and without myoepithelial differentiation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)To investigate whether salivary carcinomas with and without myoepithelial differentiation could present differences regarding degree of angiogenesis, we compared tumor vascularization between adenoid cystic (31 cases) and epithelial-myoepithelial carcinomas (14) versus mucoepidermoid (37) carcinoma. The expression of peroxiredoxin I was also studied to verify the potential relationship between cellular metabolism and microvascular density. Microvascular density for CD34 and CD105 were significantly lower in carcinomas with myoepithelial differentiation. However, no correlation was found between degree of angiogenesis and amounts of myoepithelial cells. High-grade peroxiredoxin I expression was found in 73.7% of mucoepidermoid carcinomas, whereas 85.1% of carcinomas with myoepithelial differentiation presented low-grade expression. In conclusion, carcinomas with myoepithelial differentiation, regardless of the amounts of myoepithelial cells, are associated to a significantly lower vascular density. The reasons for this lower angiogenic activity remain to be determined but could be related to metabolic characteristics of the cancer cells.4534359367Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [07/55336-2

Expression of peroxiredoxins I and IV in multiple myeloma: association with immunoglobulin accumulation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)B cell malignancies are classified according to the postulated differentiation stage of the originating cell. During differentiation, structural and molecular changes occur to support massive processing of immunoglobulin in the endoplasmic reticulum (ER) of plasma cells at the final stage. When overloaded, the ER generates unfolded proteins and hydrogen peroxide (H2O2), which may cause cell death. Peroxiredoxins (Prxs) I and IV belong to a family of proteins able to catalyze peroxide detoxification. Here, we investigated a potential association of these enzymes with immunoglobulin production in B cell neoplasms. Our results demonstrated that the expression of Prx IV was induced as cells became competent to synthesize immunoglobulin light chains, as observed by immunohistochemistry in tissue sections of B cell neoplasms and also by qPCR and Western blotting analyses in malignant B cell lines. Prx I was frequently highly expressed, indicating additional regulatory processes besides ER activity. Results obtained exclusively with myeloma cells have shown that expression of Prxs I and IV, both at mRNA and protein levels, was associated with light chain secretion quantified by ELISA. We suggest that Prxs I and IV may provide survival advantages for terminally differentiated neoplastic B cells by the elimination of H2O2 and, in the case of Prx IV, by the conversion of this toxic in a functional agent driving oxidative protein folding in the ER. In this sense, multiple myeloma and lymphomas demonstrated to synthesize immunoglobulin chains may benefit from strategic therapies targeting the adaptive pathway to ER stress, including inhibition of Prxs I and IV activity.46314755Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP