Sphingosine and Sphingosine-1-phosphate have opposite effects on the survival of retina photoreceptors

ABRAHAN CAROLINA; ROTSTEIN NORA

Cancún, México

Congreso; 21t Biennal Meeting of the International Society for Neurochemistry; 2007

Objectives:  The mediators involved in photoreceptor (Phr) apoptosis are still ill-defined. We have recently established that ceramide (Cer), a proapoptotic sphingolipid, triggers Phr apoptosis induced by oxidative stress, and docosahexaenoic acid (DHA), retina major polyunsaturated fatty acid, prevents Phr apoptosis. Here we investigated whether sphingosine (Sph) and sphingosine-1-phosphate (S1P) are involved in the regulation of Phr survival.Methods: to evaluate the effect of Sph on Phr apoptosis, rat retina neuronal cultures were treated with Sph, or, previous addition of an inhibitor of sphingosine synthesis (MAPP), with Cer or the oxidant paraquat (PQ). To investigate S1P effects, this sphingolipid was added to the cultures before treatment with PQ. To evaluate whether S1P was involved in DHA protection, cultures with or without DHA were treated with an inhibitor of sphingosine-1-kinase (DHS) and then with Cer, Sph or PQ. Nuclear integrity and mitochondrial membrane potential were determined.Results: while Sph addition induced Phr apoptosis, inhibiting its synthesis from Cer blocked apoptosis induced by addition of Cer and PQ. On the contrary, addition of S1P prevented PQ-induced apoptosis. DHA blocked Sph-induced apoptosis, whereas inhibition of sphingosine-1-kinase, which catalyzes Sph phosphorylation to S1P, before Cer, Sph or PQ treatment blocked DHA protective effect.Conclusions: These results suggest that after the increase in Cer levels induced by oxidative stress, Cer is transformed to Sph, and either Sph by itself or combined with Cer trigger Phr apoptosis. They also imply that DHA stimulates the formation of S1P, decreasing the levels of Cer and Sph to protect Phrs from oxidative damage.