Protein Carbonylation-Dependent Photoreceptor Cell Death Induced by N-Methyl-N-nitrosourea in Mice.
מילות מפתח
תַקצִיר
Retinal degenerative diseases, such as retinitis pigmentosa, are characterized by night blindness and peripheral vision loss caused by the slowly progressive loss of photoreceptor cells. A comprehensive molecular mechanism of the photoreceptor cell death remains unclear. We previously reported that heat shock protein 70 (HSP70), which has a protective effect on neuronal cells, was cleaved by a calcium-dependent protease, calpain, in N-methyl-N-nitrosourea (MNU)-treated mice retina. Carbonylated HSP70 is much more vulnerable than noncarbonylated HSP70 to calpain cleavage. However, it was not known whether protein carbonylation occurs in MNU-treated mice retina. In this study, we clearly show protein carbonylation-dependent photoreceptor cell death induced by MNU in mice. Therefore, protein carbonylation and subsequent calpain-dependent cleavage of HSP70 are key events in MNU-mediated photoreceptor cell death. Our data provide a comprehensive molecular mechanism of the photoreceptor cell death.