Vitamin E: characterization of the biological activity and relation with the nuclear receptor PPARy.
Vitamin E, a generic term to describe a group of structurally lipophilic molecules (tocopherols and tocotrienols), is one of the most known antioxidants and it has been studied also because its non-antioxidant roles. By the way, depending on the administered dose, amp;#61537;-tocopherol can exert antagonic effects in vitro. It?s known that PPARamp;#61543;, a nuclear receptor involved in transcription of inflammatory genes, can be related to amp;#61537;-tocopherol effects. Considering this, our group decided to characterize the amp;#61537;-tocopherol activity in an mice peritoneal LPS-induced inflammation model and its possible relationship with PPARamp;#61543; receptor. In this work, we show for the first time that amp;#61537;-tocopherol can exert antagonic effects in an IN VIVO inflammatory model and that anti-inflammatory activity involves KC secretion inhibition. In parallel, PPARamp;#61543; activation enhances the response in the same model, showing that this receptor exerts proinflammatory role in LPS-induced response IN VIVO. In addition, rosiglitazone, a PPARamp;#61543; agonist, upregulates KC secretion in vitro, but its activity is inhibit by amp;#61537;-tocopherol treatment. Transfection assays also show that amp;#61537;-tocopherol can act through PPARamp;#61543; signaling pathway. In conclusion, amp;#61537;-Tocopherol is an important antiinflammatory agent in LPS-induced response and its action involves down regulate of KC secretion by PPARamp;#61543; activity inhibition.
Advisor:Hugo Caire Castro Faria Neto; Adriana Ribeiro Silva
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Lipopolissacarídeos PPAR gama Tocoferóis Lipopolysaccharides Vitamin E gamma Tocopherols
Date of Publication:04/25/2007