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Evaluation of the involvement of apoptotic processes, necrotic and autophagic marrow hypoplasia in mice submitted to protein malnutrition

Grant number: 10/13329-2
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2011
Effective date (End): October 31, 2012
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Primavera Borelli Garcia
Grantee:Jackeline Soares de Oliveira Beltran
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malnutrition is a major public health problems of the world, with protein-energy malnutrition one of the most frequent. The origin of malnutrition may be due to deficiency or absence of any nutrient and that its installation depends on the cause and severity, intensity and duration of deprivation. It may be caused primarily by inadequate diet, or secondarily by deficient intake or poor absorption and by increased usage or by excessive excretion of protein restriction nutrient.A modifies physiological responses can induce cell injury, so mechanisms involved in proliferation, differentiation and cell death may change in malnutrition, which affects differently the different tissues. The high and constant need of proteins by tissue hematopoietic makes it against the common hematological abnormalities such as anemia and leukopenia in malnutrition and quantitative hematological anemia, leukopenia, neutropenia and lymphocytopenia are a reflection of the involvement of lymph organs hematopoietic-under conditions of malnutrition and are associated with modification of immune response which results in greater susceptibility to infection. Studies in our laboratory has shown, protein malnutrition, hypoplastic bone marrow of mice with histologic evidence of alteration of ECM (extracellular matrix cell). Protein malnutrition on some studies have shown that nutritional imbalances can readily induce cell death (apoptosis) which is a type of cellular self-destruction, physiological in nature, which requires energy and protein synthesis for its execution, may also induce a necrosis that is related to severe aggression and lead to sharp decline in the production of ATP in the membrane or injury such as hypoxia, ischemia, among others, and also occurs in diseases related to inborn errors of metabolism and imbalances nutricionais.A all times our cells are digested and renewing, reusing and disposing proteins through a biological mechanism called autophagy. Seen before only as a cell death process, this form of selective self-destruction of cellular components show up as a device for survival of organisms. Autophagy can be stimulated in certain situations, such as: hunger and nutritional imbalances and metabolic . When these conditions is induced by autophagy maintains a pool of amino acids essential for protein can be synthesized is a form of programmed cell death in which the cell digests some of its own organelles providing the necessary nutrients. Understanding the interaction between these different forms of cell death and unbalanced nutrition is important because of its deep impact on development, growth and immune function. In view of the foregoing and considering the previous results from our group showed evidence that protein malnutrition leads to impaired hemopoese, peripheral pancytopenia with marrow hypoplasia, changes in the extracellular matrix, presence of stem / progenitor cells in the G0/G1 phase of cell cycle, increased plasma concentrations of glucocorticoids and reduced insulin and IGF1, we propose in this project to evaluate the involvement of apoptotic processes, necrotic and autophagic hypoplasia outlined above.