Evaluation of the effects of PTEN compartmentalization in human cells of glioblastoma (U87MG) submitted to a inflammatory stimuli

• Grant number: 16/07376-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2016
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Amanda Galvão da Paixão
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Evidences have expanded the concept that neuroinflammation is a causal and exacerbating component of neurodegenerative diseases. As resident cell of immune system in central nervous system (CNS), microglia acts as sensitive element and primary defense line against pro-inflammatory stimuli. Is is now becoming clear that the release of pathological levels of cytotoxic substances, such as extracellular debris, high levels of pro-inflammatory cytokines with concomitant oxidative stress in combination with activation factors and recruitment of microglia support their role on neurodegenerative diseases. Although originally describe as tumor suppressor, PTEN (phosphatase and tensin homolog) has been studied in various cellular processes such as growth, survival, proliferation, metabolism and cellular migration, with a potential modulatory role on neurogenesis, synaptic plasticity and, more recently, on inflammation. PTEN localization can be both nuclear and cytoplasmic and its functions seem to depend on its cellular compartmentalization. This project will focus on the role of PTEN on neuroinflammation and aim to study the possible effects of PTEN compartmentalization (nucleus/cytoplasm) in front of inflammation induced by lipopolysaccharide (LPS) on the U87MG lineage derived of human glioma. The insights of the involvement of PTEN on the pathways and molecular mechanisms direct and indirectly related to neuroinflammation can lead to the development of new therapeutic strategies for more effective treatments against diseases associated to PTEN deletion and mutation, neuroinflammation and neurodegenerative diseases. As a pioneer study in this area, the data obtained from this study will be of great impact to the neuroscience and for the treatment of neuropsychiatric diseases. (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)

KINOSHITA, PAULA F.; YSHII, LIDIA M.; ORELLANA, ANA MARIA M.; PAIXAO, AMANDA G.; VASCONCELOS, ANDREA R.; LIMA, LARISSA DE SA; KAWAMOTO, ELISA M.; SCAVONE, CRISTOFORO. Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells. SCIENTIFIC REPORTS, v. 7, JUL 7 2017. (11/22844-0, 11/10303-5, 14/05026-0, 16/07376-4, 11/21308-8, 11/12255-8, 11/04327-9)

VASCONCELOS, ANDREA R.; DA PAIXAO, AMANDA G.; KINOSHITA, PAULA F.; ORELLANA, ANA M.; SCAVONE, CRISTOFORO; KAWAMOTO, ELISA M.. Toll-like Receptor 4 Signaling is Critical for the Adaptive Cellular Stress Response Effects Induced by Intermittent Fasting in the Mouse Brain. Neuroscience, v. 465, p. 142-153, JUN 15 2021. (14/01435-3, 19/12974-6, 16/22996-9, 16/07376-4, 06/57729-9, 16/07427-8, 11/12255-8, 09/11915-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PAIXÃO, Amanda Galvão da. Effects of PTEN inhibition over neuroinflammation in glial cells.. 2018. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.