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Methionine sulfoxide reductases (MSRs) are expressed in vascular smooth muscle cells and increase their resistance against oxidative stress
Author(s) -
Haenold Ronny,
Wassef Ramez,
Hoshi Toshinori
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1073-a
Subject(s) - msra , methionine sulfoxide reductase , oxidative stress , viability assay , vascular smooth muscle , methionine , oxidative phosphorylation , apoptosis , reactive oxygen species , biology , biochemistry , microbiology and biotechnology , chemistry , endocrinology , amino acid , smooth muscle
Most cell types are protected against oxidative stress caused by reactive species (RS) with antioxidant compounds or enzymes, however such treatment inhibits RS‐triggered signaling and induces apoptosis in vascular smooth muscle cells (VSMC). Here we test the hypothesis that methionine sulfoxide reductases, which reduce oxidized methionine (met‐O) back to met, are expressed in VSMC and protect them against oxidative damage. Endogenous expression of msrA and msrB2 in rat A‐10 VSMC was analyzed by RT‐PCR amplification. We detected both msr transcripts and identified two new splicing forms of msrA in VSMC. To test that enhanced activity of MSRA and MSRB2 influences VSMC viability as measured by MTT assay, we transiently overexpressed different enzyme variants by adenoviral infection. Overexpression of MSR enzymes did not change the basal cell viability of non‐stressed cells. Oxidative stress was generated by treatment with the met‐preferring oxidizing reagent chloramine‐T (ChT). Among the MSR variants, the most effective protection was detected with cytoMSRA, distinctly followed by mitoMSRA, mitoMSRB2, and a cytoplasmic targeted fusion MSRB‐A. Cytoplasmic localized MSRA effectively increases the resistance against ChT‐induced oxidative stress without affecting the basal VSMC viability and may be a tool to attenuate age‐associated accumulation of oxidative damage in vasculature. Supported by NIH and Parkinson's Disease Foundation.