Mechanisms of Retinal Diseases Section, Laboratory of Retinal Cell and Molecular Biology, National eye institute, NIH, 6 Center Drive, MSC 0608 Bldg. 6 Bethesda, MD 20892, USA.
Exp Eye Res. 2010 Mar;90(3):420-8. doi: 10.1016/j.exer.2009.12.003. Epub 2009 Dec 22.
Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial enzyme that converts methionine sulfoxide (R) enantiomer back to methionine. This enzyme is suspected of functioning to protect mitochondrial proteins from oxidative damage. In this study we report that the retina is one of the human tissues with highest levels of MSRB2 mRNA expression. Other tissues with high expression were heart, kidney and skeletal muscle. Overexpression of an MSRB2-GFP fusion protein increased the MSR enzymatic activity three-fold in stably transfected cultured RPE cells. This overexpression augmented the resistance of these cells to the toxicity induced by 7-ketocholesterol, tert-butyl hydroperoxide and all-trans retinoic acid. By contrast, knockdown of MSRB2 by a miRNA in stably transfected cells did not convey increased sensitivity to the oxidative stress. In the monkey retina MSRB2 localized to the ganglion cell layer (GLC), the outer plexiform layer (OPL) and the retinal pigment epithelium (RPE). MSRB2 expression is most pronounced in the OPL of the macula and foveal regions suggesting an association with the cone synaptic mitochondria. Our data suggests that MSRB2 plays an important function in protecting cones from multiple type of oxidative stress and may be critical in preserving central vision.
甲硫氨酸亚砜还原酶 B2（MSRB2）是一种线粒体酶，可将甲硫氨酸亚砜（R）对映体还原回甲硫氨酸。该酶被怀疑具有保护线粒体蛋白免受氧化损伤的功能。在这项研究中，我们报告说，视网膜是人组织中 MSRB2 mRNA 表达水平最高的组织之一。其他高表达的组织有心、肾和骨骼肌。MSRB2-GFP 融合蛋白的过表达使稳定转染的培养 RPE 细胞中的 MSR 酶活性增加了三倍。这种过表达增强了这些细胞对 7-酮胆固醇、叔丁基过氧化物和全反式视黄酸诱导的毒性的抵抗力。相比之下，通过 miRNA 在稳定转染的细胞中敲低 MSRB2 并没有导致对氧化应激的敏感性增加。在猴视网膜中，MSRB2 定位于神经节细胞层（GCL）、外丛状层（OPL）和视网膜色素上皮（RPE）。MSRB2 的表达在黄斑和中央凹区域的 OPL 中最为明显，提示其与锥体细胞突触线粒体有关。我们的数据表明，MSRB2 在保护锥体免受多种类型的氧化应激方面发挥着重要作用，对于保护中心视力可能至关重要。
