Over-expression of methionine sulfoxide reductase A in the endoplasmic reticulum increases resistance to oxidative and ER stresses.
MsrA and MsrB catalyze the reduction of methionine-S-sulfoxide and methionine-R-sulfoxide, respectively, to methionine in different cellular compartments of mammalian cells. One of the three MsrBs, MsrB3, is an endoplasmic reticulum (ER)-type enzyme critical for stress resistance including oxidative and ER stresses. However, there is no evidence for the presence of an ER-type MsrA or the ER localization of MsrA. In this work, we developed an ER-targeted recombinant MsrA construct and investigated the potential effects of methionine-S-sulfoxide reduction in the ER on stress resistance. The ER-targeted MsrA construct contained the N-terminal ER-targeting signal peptide of human MsrB3A (MSPRRSLPRPLSLCLSLCLCLCLAAALGSAQ) and the C-terminal ER-retention signal sequence (KAEL). The over-expression of ER-targeted MsrA significantly increased cellular resistance to H2O2-induced oxidative stress. The ER-targeted MsrA over-expression also significantly enhanced resistance to dithiothreitol-induced ER stress; however, it had no positive effects on the resistance to ER stresses induced by tunicamycin and thapsigargin. Collectively, our data suggest that methionine-S-sulfoxide reduction in the ER compartment plays a protective role against oxidative and ER stresses.
Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717, Korea.
Jung-Yeon
JY
Kim
Yongjoon
Y
Kim
Geun-Hee
GH
Kwak
Su Young
SY
Oh
Hwa-Young
HY
Kim
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress
D051150:Methionine Sulfoxide Reductases
MsrA; endoplasmic reticulum; methionine sulfoxide reductase; stress resistance