Activation of DE NOVO síntesis of ceramide induces photoreceptors apoptosis.

MIRANDA G; ABRAHAN C; GERMAN L; ROTSTEIN N

Pinamar, Buenos Aires, Argentina,

Congreso; X Congress PABMB, XLI Annual Meeting of the Argentine SAIB and XX Annual Meeting of SAN; 2005

ACTIVATION OF DE NOVO SYNTHESIS OF CERAMIDE  INDUCES PHOTORECEPTOR APOPTOSIS Miranda, Gisela; Abrahan, Carolina; German, Lorena and Rotstein Nora. INIBIBB, UNS-CONICET, Bahía Blanca, Argentina. E-mail: gmiranda@criba.edu.ar The precise mechanisms leading to photoreceptor death in the retina are still unknown. We investigated whether an increase in ceramide, a sphingolipid known to trigger apoptosis upon cellular stress, activates apoptosis in rat retina photoreceptors in culture. Paraquat (PQ)-induced oxidative stress led to the accumulation of newly synthesized [3H]ceramide in photoreceptors, which almost doubled the amount found in controls 2 and 4 hs after PQ addition, but did not affect the amount of [3H]sphingomyelin. Ceramide increase was parallel to the onset of photoreceptor apoptosis. We previously showed that inhibiting ceramide synthesis with fumonisin B1 (FB) prevented photoreceptor apoptosis upon PQ addition. To confirm those results and establish which pathway is involved in ceramide synthesis, we treated cultures with cycloserine, which blocks the first step in ceramide synthesis, 30 min before PQ treatment; this addition completely blocked PQ-induced photoreceptor apoptosis. FB addition at day 0 partially diminished photoreceptor apoptosis by day 6 in vitro, which otherwise occurred in the absence of photoreceptor trophic factors. These results suggest that an increase in ceramide levels triggers photoreceptor apoptosis in different situations of cellular stress, and that this increase arises in the stimulation of de novo synthesis of ceramide.