Increased viability of PC12 cells exposed to amyloid-beta 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 1 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 PC12 cells, where it showed enzymatic activity. We showed that transduction of TAT-MsrA increased cell viability and reduced DNA fragmentation in PC12 cells treated with amyloid-beta (A beta). We suggest that MsrA transduction could reduce the oxidative damage caused to cellular proteins by A beta and could play a role in the treatment of Alzheimer's disease.
Jung
Bomi
B
Graduate School of East-West Medical Science, Kyung-Hee University, Yong-In, Korea.
Lee
Eunjoo H
EH
Chung
Woo-Sook
WS
Lee
Seung Jae
SJ
Shin
Seung-Hun
SH
Joo
Se-Hwan
SH
Kim
Seong-Ki
SK
Lee
Joon H
JH
D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D053938:DNA Fragmentation / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics*; D006801:Humans; D051150:Methionine Sulfoxide Reductases; D010088:Oxidoreductases / Q000235:genetics*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods*
D016229:Amyloid beta-Peptides; D015696:Gene Products, tat; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase