Intracelular Pathways Involved in the Antiapoptotic Effect of Trophic Factors in Retinal Neurons.

GERMAN L; ROTSTEIN N; POLITI L

Buenos Aires, Argentina

Congreso; Reunión Conjunta de la Sociedad Internacional de Neuroquímica (ISN) y la Sociedad Americana de Neuroquímica (ASN).; 2001

  INTRACELLULAR PATHWAYS INVOLVED IN THE ANTIAPOPTOTIC EFFECT OF TROPHIC FACTORS IN RETINAL NEURONS German L., Rotstein N. and Politi L. Instituto de Investigaciones Bioquímicas. CC 857. 8000 B. Blanca, Argentina. e-mail: inpoliti@criba.edu.ar    We have previously demonstrated that in the absence of trophic factors, retinal neurons in vitro die through apoptotic pathways. Their survival depends on specific trophic factors: docosahexaenoic acid (DHA) postpones the onset of photoreceptor apoptosis, while insulin like growth factor-I (IGF-I) prevents the apoptosis of amacrine cells. In this work we studied the intracellular pathways that take part in the protective mechanisms of these factors. In photoreceptor cells, the progression of apoptosis corresponded with a decrease in the percentage of their functional mitochondria while fragmentation of lamins A and C, components of the nuclear lamina, occurred at late stages during the advance of photoreceptor apoptosis. DHA addition decreased apoptosis, simultaneously protecting mitochondria functionality and lamin integrity. Expression of the anti-apoptotic protein Bcl-2 increased upon DHA supplementation. In amacrine neurons, IGF-I prevented the loss of mitochondrial activity that accompanied their apoptosis in cultures lacking this trophic factor and preserved the integrity of lamins, which were otherwise fragmented at a late phase in the apoptotic pathway. These results suggest that disintegration of the nuclear lamina is a late event during neuronal apoptosis; on the contrary, a close correlation seems to exist between apoptosis progression and the outset of alterations in mitochondrial integrity. Both DHA and IGF-I act as survival signals, activating intracellular mechanisms leading to the preservation of mitochondrial functionality and lamin integrity as part of their antiapoptotic effect.