Over-expression of methionine sulfoxide reductase A in the endoplasmic reticulum increases resistance to oxidative and ER stresses

• Published in: Acta biochimica et biophysica Sinica 2014-05, Vol.46 (5), p.415-419
• Main Authors: Kim, Jung-Yeon, Kim, Yongjoon, Kwak, Geun-Hee, Oh, Su Young, Kim, Hwa-Young
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cell Line; Endoplasmic Reticulum - enzymology; Endoplasmic Reticulum - metabolism; Humans; Methionine Sulfoxide Reductases - chemistry; Methionine Sulfoxide Reductases - metabolism; Mice; Molecular Sequence Data; Oxidative Stress; 亚砜; 内质网应激; 哺乳动物细胞; 应力; 抗氧化; 甲硫氨酸; 过表达; 还原酶
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmu011

MsrA and MsrB catalyze the reduction of methionine-S- suifoxide 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 local- ization 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 H202-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.