Identification of a new functional splice variant of the enzyme methionine sulphoxide reductase A (MSRA) expressed in rat vascular smooth muscle cells
Identification of a new functional splice variant of the enzyme methionine sulphoxide reductase A (MSRA) expressed in rat vascular smooth muscle cells
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DOI：
10.1080/10715760701642096
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Hoshi, Toshinori
中科院分区：
文献类型：
--
作者：
Haenold, Ronny;Wassef, Ramez;Hoshi, Toshinori
活性氧有助于血管系统的老化和心血管疾病的发展。甲硫氨酸-S-亚砜是甲硫氨酸的氧化形式，由甲硫氨酸亚砜还原酶A（MSRA）修复。这种酶通过选择性剪接靶向线粒体或细胞溶质，对抗氧化应激至关重要。本研究旨在检测大鼠主动脉血管平滑肌细胞（VSMCs）中MSRA的内源性表达和细胞内定位。我们检测到强大的MSRA免疫反应性只在线粒体。msrA转录本的序列分析揭示了一种新的线粒体剪接变异体，msrA 2a，在培养的大鼠VSMCs以及主动脉组织制剂的存在。重组MSRA 2a蛋白的酶活性通过模型底物肽中甲硫氨酸亚砜的还原来证实。我们的结论是，多个MSRA变体参与修复氧化蛋白在VSMC线粒体，但其他保护机制可能存在于细胞质隔室。
Reactive oxygen species contribute to ageing of the vascular system and development of cardiovascular disease. Methionine-S-sulphoxide, an oxidized form of methionine, is repaired by the enzyme methionine sulphoxide reductase A (MSRA). The enzyme, targeted to mitochondria or the cytosol by alternative splicing, is vital for oxidative stress resistance. This study was designed to examine the endogenous expression and intracellular localization of MSRA in rat aortic vascular smooth muscle cells (VSMCs). We detected robust MSRA immunoreactivity exclusively in mitochondria. Sequence analysis of msrA transcripts revealed the presence of a novel mitochondrial splice variant, msrA2a, in cultured rat VSMCs as well as in aortic tissue preparations. The enzymatic activity of a recombinant MSRA2a protein was confirmed by the reduction of methionine sulphoxide in a model substrate peptide. We conclude that multiple MSRA variants participate in the repair of oxidized proteins in VSMC mitochondria, but that other protective mechanisms may exist in the cytoplasmic compartment.