Slide 1: Evidence for the Involvement of PPARs in the Photoprotective Activity of BIO201 (Norbixin) on RPE
EVIDENCE FOR THE INVOLVEMENT OF PPARs IN THE PHOTOPROTECTIVE ACTIVITY OF BIO201 (NORBIXIN) ON RETINAL PIGMENT EPITHELIUM. Fontaine V.1, Monteiro E.1, Fournie M.1, On S.2, Serova M.2, Dilda P.2 and Lafont R.2 1 Sorbonne Universités, UPMC Univ. Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Mor
Slide 2: Introduction
INTRODUCTION According to Herzlich (PPAR Res. 2008 Article ID 389507 ), PPARs play a key role in the protection of RPE cells against Age-Related Macular Degeneration (AMD) PPARs comprise three subtypes that can accommodate various types of ligands. The aim of the present work was to investigate the
Slide 3: A2E reduces PPARa levels; BIO201 blunts the effect
A2E sensitizes RPE cells to blue light damage and reduces PPARa protein levels. Both effects are blunted by BIO201, a preparation of the diapo- carotenoid norbixin developed by Biophytis1. No significant effect is observed on other PPARs levels. PPARa PPARb/d PPARg relative expression compared to DM
Slide 4: BIO201 (norbixin) activates hPPARa and more efficiently hPPARb/d
BIO201(norbixin) activates hPPARa and even more efficiently hPPARb/d Day 1 Day 2 Day 3 Day 4 Cell plating into 96- CV1 cell plating Cell transfection with pG5TkpGI3 well dark plate into flask (reporter vector) & pGal4-hPPAR (morning) Norbixin treatment Luciferase activity (afternoon) measurement hPP
Slide 5: Effect of various pharmacological agents
DIRECT BINDING TESTS (competition with radioactive ligands): BIO201 (norbixin) binds to PPARa with a Ki of 16.5 µM, and to PPARg with a Ki of 1.15 µM FRET ACTIVITY TESTS (induction of PPAR coactivator or corepressor recruitment): BIO201 (norbixin) shows no agonist effect on any of the three PPARs, b
Slide 6: Conclusions
CONCLUSIONS • These experiments have revealed the difficulty of interpreting experimental data, arising from the limited specificity of current PPAR agonists and antagonists, a potential source of multiple cross-reactions (e.g. troglitazone). • There is some discrepancy between activation studies an