Unfolded protein response-induced dysregulation of calcium homeostasis promotes retinal degeneration in rat models of autosomal dominant retinitis pigmentosa.

ABSTRACT: The molecular mechanism of autosomal dominant retinitis pigmentosa (ADRP) in rats is closely associated with a persistently activated unfolded protein response (UPR). If unchecked, the UPR might trigger apoptosis, leading to photoreceptor death. One of the UPR-activated cellular signaling culminating in apoptotic photoreceptor cell death is linked to an increase in intracellular Ca(2+). Therefore, we validated whether ADRP retinas experience a cytosolic Ca(2+) overload, and whether sustained UPR in the wild-type retina could promote retinal degeneration through Ca(2+)-mediated calpain activation. We performed an ex vivo experiment to measure intracellular Ca(2+) in ADRP retinas as well as to detect the expression levels of proteins that act as Ca(2+) sensors. In separate experiments with t

SUBMITTER: Shinde V 

PROVIDER: S-EPMC4670931 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature