Retina-derived endogenous sulfur dioxide might be a novel anti-apoptotic factor

Highlights: • Endogenous SO₂ existed in the mouse retinal tissue and photoreceptor cell. • Oxidative stress inhibited endogenous SO₂ generation in the photoreceptor cell. • Deficiency of endogenous SO₂ might be involved in the photoreceptor cell apoptosis. Endogenous sulfur dioxide (SO₂) was found to be generated from the enzymatic reaction catalysed by aspartate transference 1 (AAT1) in the mammals and play importantly biological effects. In the present study, we explored the existence of endogenous SO₂ pathway in mouse retinal tissues and 661w photoreceptor cell and investigated its possible pathophysiological role in the hydrogen peroxide (H₂O₂)-induced mouse photoreceptor cell apoptosis. The data showed that endogenous SO₂ pathway including AAT1 expression and SO₂ content was found to be presented in mouse photoreceptor cells. AAT1 protein and SO₂ were mainly distributed in the cytoplasm, while a small amount of AAT1 protein and SO₂ was found in the nucleus of 661W photoreceptor cells. H₂O₂ significantly decreased the SO₂ content and AAT1 expression, but increased the cleaved caspase-3 protein level and the apoptotic index, and the number of TUNEL-positive cells in the 661W photoreceptor cells. Moreover, an AAT inhibitor HDX treatment inhibited SO₂ synthesis and mimicked H₂O₂-induced apoptosis in 661W cells. In conclusion, the endogenous SO₂/AAT1 pathway is firstly found to be present in mouse photoreceptor cells, and might play an important role in the prevention from mouse photoreceptor cell apoptosis.