Changes in LPS induced gene expression by Klotho protein in cultured cerebellar cells

• Grant number: 13/08438-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2013
• End date: September 13, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Thaís Neves Sala
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Change of Klotho protein is associated with a marked decrease in life expectancy, and the early onset of diseases and syndromes related to aging, such as arteriosclerosis, osteoporosis, skin atrophy, pulmonary emphysema and cognitive decline, whereas its overexpression increases around 30% life expectancy. Studies suggest the presence of an interaction between Klotho, TNF-±, NF-KB and inflammation signaling cascade in kidneys and endothelial cells. Thus, is relevant to determine the function of this protein in inflammatory signaling triggered by LPS in the central nervous system (CNS) since neuroinflammation is present in neurodegenerative diseases such as Parkinson's disease and Alzheimer's. The Klotho is an endogenous protein that is able to provide an anti-inflammatory and protective action in renal cells by inhibiting activation of NF-KB and the subsequent production of inflammatory cytokines in response to stimulation of TNF-±. The interaction between Klotho, TNF-±, NF-KB and inflammatory processes is not restricted to the kidney, since the Klotho appears to protect endothelial cells in inflammation, suppressing the development of atherosclerosis in the vascular system. This project aims to evaluate the effects of Klotho protein in primary mixed neuron-astrocyte in the cerebellum of mice in the presence and absence of inflammatory stimulus (LPS - 1 ug / ml) which is a bacterial endotoxin. We intend to evaluate the changes induced by Klotho in LPS induced activation of NF-KB and modulation of certain genes linked to the inflammatory response and / or apoptosis in primary culture of mixed neuron-astrocyte cerebellum. (AU)