Molecular pathways involved in the antiapoptotic effect of docosahexaenoic acid on retina photoreceptors

POLITI L; ROTSTEIN N; GERMAN L

Bergen , Noruega

Congreso; 42nd International Conference on the Bioscience of Lipids; 2001

Molecular pathways involved in the antiapoptotic effect of docosahexaenoic acid on retina photoreceptors Politi L., Rotstein N. and German L. Instituto de Investigaciones Bioquímicas  y Universidad Nacional del Sur. CC 857. 8000 Bahía Blanca, Argentina. inpoliti@criba.edu.ar We have previously shown that rat retina photoreceptors depend on docosahexaenoic acid (DHA) for their survival and differentiation; however, the molecular mechanisms involved in this protective effect remain unknown. In cultures lacking trophic factors, an increase in photoreceptor apoptosis runs parallel with a decrease in the percentage of their functional mitochondria; on the contrary, fragmentation of lamins A and C, components of the nuclear lamina, was only visible after 9 days in culture. DHA decreased photoreceptor apoptosis, simultaneously preventing lamin fragmentation and protecting mitochondria functionality: by day 11, only 10% of photoreceptors retained active mitocondria in control cultures, while this percentage raised to about 40% upon DHA supplementation. DHA addition also stimulated the expression of the anti-apoptotic protein bcl-2. These results demonstrate that disintegration of the nuclear lamina is a late event during photoreceptor apoptosis, while a close correlation exists between apoptosis progression and the outset of alterations in mitochondrial integrity. They also suggest that DHA, as other trophic factors, activates one or several intracellular pathways and upregulation of bcl-2 expression is probably among the first steps of its antiapoptotic effect. Preservation of mitochondrial functionality through this increase in bcl-2 levels or by a direct regulation of mitochondrial membrane properties appears to be crucial for the accomplishment of DHA protective effect on photoreceptor cells.