Functional proteomics: mechanisms of action of new drugs, cellular stress and the role of Unfold Protein Response (UPR ) of the endoplasmic reticulum proteins in glioblastoma cell lines.

• Grant number: 16/10632-2
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2016
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: José César Rosa
• Grantee: José César Rosa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Clarice Izumi ; Hélen Julie Laure ; Norberto Peporine Lopes ; Sueli Mieko Oba Shinjo ; Suely Kazue Nagahashi Marie

Abstract

Glial cells (astrocytes, oligodendrocytes, microglia and ependymocytes), the most numerous in the human brain, provide nutritional support, blood, structural and defense to neurons. They can mutate giving rise to glial tumor cells or glioma, of which 70% are derived from astrocyte cells. The development of tumors is often attributed to an accumulation of genetic changes that allow cells to escape the normal control of proliferation, apoptosis and cell migration. Our group has demonstrated the involvement of heat shock proteins like GRP78 involved in UPR and HSPB1 / HSP27 which have major impact on survival of patients with GBM. Molecular chaperone proteins are considered to be key in maintaining the proteome, since it facilitates the folding of nascent polypeptides, as well as the folding and / or degradation of misfolded proteins. The expression and activity of molecular chaperones are tightly regulated both at transcriptional and posttranslational level in the state of increased oxidative body and consequently the proteotoxic stress, including the state of aging and related diseases such as cancer. To achieve this objective, we plan to investigate: 1) The role of heat shock proteins in cellular stress and UPR on cell glioblastoma cell lines through proliferation assays, cell migration, changes in the proteome based on mass spectrometry and Western blotting validation; 2) Cell intercommunication: Isolation and characterization of proteomic profile of exosomes derived from strains of glioblastoma cell under stress conditions and 3) Mechanisms of action of new drugs isolated from natural products, AM04 and AM05, compared to temozolomide action. With these proteomic approaches and biological processes is expected to contribute to the achievement of new drugs and increase knowledge of cancer biology. (AU)

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)

IZUMI, CLARICE; LAURE, HELEN JULIE; BARBOSA, NAYARA GONCALVES; HASSIBE THOME, CAROLINA; AGUIAR FERREIRA, GERMANO; PAULO BARRETO SOUSA, JOAO; PEPORINE LOPES, NORBERTO; CESAR ROSA, JOSE. Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthusspp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 13, JUL 2020. (16/10632-2)