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Study of Peroxiredoxin 4 in multiple Myeloma cells exposed to agents that promote endoplasmic reticulum stress

Grant number: 14/21823-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2015
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Ana Paula Dias Demasi
Grantee:Gustavo Rodrigues da Cunha
Home Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil
Associated research grant:09/52200-8 - Study of the function of peroxiredoxins I and IV in myeloma cells: evaluation of their potential as therapeutic targets, AP.JP

Abstract

Multiple myeloma is an incurabel neoplasia of monoclonal plasma cells, derived from the B cells of the bone marrow, capable of infiltrating the surrounding bone tissue, causing lytic lesion. These cells produce large amounts of a single monoclonal (M) protein, which induces a higher functional activity of the kidneys that may cause the collapse of these organ. Characteristically, this production overloads the endoplasmic reticulum (ER) processing machinery, causing accumulation of unfolded proteins and reactive oxygen species in this organelle. Cells respond to this forms of stress by activating adaptative pathways collectively known as the Unfolded Protein Response (UPR), essential to the survival of multiple myeloma cells and widely explored as therapeutic target for this neoplasia. Peroxiredoxins are versatile proteins that are capable of eliminating reactive oxygen species and also act as molecular chaperones. They are overexpressed in multiple mieloma cells, and the isoform Prdx 4 represents the member of this family found manly in the ER.Our intention is to assess Prdx 4 expression in the multiple myeloma cells exposed to agents that induce ER stress, thus evaluating its participation in the UPR. We believe that this project can help to improve our understanding about the defense mechanisms of multiple myeloma cells that assure their survival, and also for the identification of theraupetic targets, in special Prdx4.

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