Over-expression of methionine sulfoxide reductase A in the endoplasmic reticulum increases resistance to oxidative and ER stresses
- Over-expression of methionine sulfoxide reductase A in the endoplasmic reticulum increases resistance to oxidative and ER stresses
- 김화영; 김정연; 김용준; 곽근희; 오수영
- SMOOTH-MUSCLE-CELLS; SUBCELLULAR-LOCALIZATION; SACCHAROMYCES-CEREVISIAE; A MSRA; DROSOPHILA; MECHANISM; RESIDUES; ENZYMES; GENE
- Issue Date
- OXFORD UNIV PRESS
- ACTA BIOCHIMICA ET BIOPHYSICA SINICA, v.46, no.5, pp.415 - 419
- 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.
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