Increased viability of PC12 cells exposed to amyloid-β peptide by transduction with human TAT-methionine sulfoxide reductase

Methionine sulfoxide reductase (MsrA) catalyzes the reduction of methionine sulfoxide to methionine, which is able to scavenge oxidatively damaged proteins. Oxidative stress has been linked to the pathophysiology of Alzheimer's disease, and a decrease in MsrA activity has also been implicated in Alzheimer's disease. The transactivator of transcription (TAT) protein from human immunodeficiency virus I has been used to deliver full-length proteins into mammalian cells. We produced genetic in-frame TAT-MsrA fusion protein and successfully transduced it into PCl2 cells, where it showed enzymatic activity. We showed that transduction of TAT-MsrA increased cell viability and reduced DNA fragmentation in PCl2 cells treated with amyloid-beta (Abeta). We suggest that MsrA transduction could reduce the oxidative damage caused to cellular proteins by Abeta and could play a role in the treatment of Alzheimer's disease. (C) 2003 Lippincott Williams Wilkins.