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Study of the function of peroxiredoxins I and IV in myeloma cells: evaluation of their potential as therapeutic targets

Abstract

Multiple myeloma (MM) is an incurable blood cancer that occurs in the bone marrow, characterized by clonal expansion of plasma cells, usually accompanied by persistent production of a single type of immunoglobulin. This production overloads the processing machinery of the endoplasmic reticulum, causing accumulation of unfolded proteins and increase of reactive oxygen species (ROS). Cellular defense systems for these specific forms of stress have been explored as therapeutic targets for MM. Peroxiredoxin (Prx) I is highly expressed in myeloma cells. This protein belongs to a family of abundant enzymes, collectively called Prxs, which can act in the removal of ROS and also as molecular chaperones. Prx I is the most abundant isoform and is located in the cytoplasm, whereas Prx IV is distributed in the endoplasmic reticulum. We want to evaluate the involvement of Prxs I and IV in the protection of myeloma cells against different types of stress, studying: a) their expression in plasma cells isolated from patients affected by the disease and possible correlation with prognostic factors; b) their oligomerization state; c) effect of their corresponding genes silencing in parameters related to the cell viability, redox homeostasis, the endoplasmic reticulum stress, production and secretion of immunoglobulins; c) effect, in these same parameters, of their corresponding gene silencing associated with exposure to drugs that stimulate oxidative stress or to proteassome inhibitors. This project can contribute to better understanding of the protection mechanisms employed by myeloma cells and to identify possible therapeutic targets. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DUARTE, POLIANA M.; NAPIMOGA, MARCELO H.; FAGNANI, ELLEN C.; SANTOS, VANESSA R.; BASTOS, MARTA F.; RIBEIRO, FERNANCLA V.; ARAUJO, VERA C.; DEMASI, ANA PAULA D. The expression of antioxidant enzymes in the gingivae of type 2 diabetics with chronic periodontitis. ARCHIVES OF ORAL BIOLOGY, v. 57, n. 2, p. 161-168, FEB 2012. Web of Science Citations: 8.

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