Expression of PGC-1 transcription factor coactivator during immune response to bacteria

• Grant number: 07/07897-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2008
• Effective date (End): December 31, 2008
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Heraldo Possolo de Souza
• Grantee: Paola Celina de Carvalho Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

PGC-1 alfa and beta are transcription coactivators, a new class of proteins that, although they do not bind directly to DNA, may control the genetic response. PGC-1 can bind to several transcription factors, leading to increased expression of genes involved in mitochondrial biogenesis and respiratory function. This response can cause enhanced enzymatic fatty acids oxidation, Krebs cycle activity and oxidative phosphorylation. Increased PGC-1 expression occurs when there is an increased energy demand, like during aerobic exercise. PGC-1 knockout animals are intolerant to exercise and present cardiac dysfunction under stress conditions. During the inflammatory response, mainly when phagocytosis is involved, there is an increase in oxygen consumption by the leukocytes, due to superoxide generation as well as to an enhanced mitochondrial function. Therefore, it is our objective to determine whether modulation of PGC-1 expression occurs during the macrophage response to bacteria. Initially, human and murine macrophages in culture will be exposed to bacteria and either the phagocytosis (by fluorescence assays) and PGC-1 expression (by real time PCR) will be measured along a timeline. To verify whether the same phenomenon occurs in vivo, mice will be innoculated with living bacteria intraperitoneally and the expression of PGC-1 in macrophages will be monitored. we believe that data obtained will be useful in detemining new mechanisms for controlling the innate immune function and, maybe, suggest new antiinflammatory therapeutic targets .