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W. M. Cleghorn, S. Kook, E. V. Gurevich, V. V. Gurevich; Caspase Cleavage of Arrestin1 in Photoreceptor Apoptosis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5436.
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To determine the possible role of arrestin1 cleavage products in photoreceptor cell death.
Arrestin1 cleavage by caspases was evaluated in vitro and in vivo in etoposide-treated Rat-1 cells. The cell lysates were analyzed for arrestin1 cleavage products, and their distribution in the cell was determined by fractionation.
Prolonged exposure of mice to intense light induces apoptosis of photoreceptor cells, accompanied by the cleavage of endogenous arrestin1. To determine whether this cleavage results from the activation of caspases, we tested whether arrestin1 was cleaved in vitro using purified arrestin1 with recombinant caspases in the presence and absence of P-Rh*. Indeed, we found that both bovine and mouse arrestin1 are cleaved in the presence of P-Rh*, but not in the absence of the receptor. The fragments generated from both proteins were comparable in size. Bovine arrestin1 was also cleaved in apoptotic Rat-1 cells. The cleavage sites were identified as 364D, 397D, and 403D by mutagenesis of individual aspartic acid residues in the C-terminus of the protein. Previously we found that, in contrast to full-length protein, the caspase-generated arrestin2 fragment localizes to the mitochondria, and induces the release of cytochrome C in apoptotic Rat-1 cells. Similarly, caspase-generated bovine arrestin1 fragment also preferentially localizes to the mitochondria under these conditions. Interestingly, arrestin4 was not cleaved by caspases either in vitro or in vivo.
Arrestin1 cleaved by caspases likely plays a role in apoptotic cell death of photoreceptor cells.
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