Methionine Sulfoxide Reductases Relevance to Aging and Protection against Oxidative Stress
Methionine Sulfoxide Reductases Relevance to Aging and Protection against Oxidative Stress
复制标题
DOI：
10.1196/annals.1354.006
复制
发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Petropoulos, Isabelle
中科院分区：
文献类型：
--
作者：
Cabreiro, Filipe;Picot, Cedric R.;Petropoulos, Isabelle
蛋白质易受活性氧（ROS）修饰，特定氨基酸残基的氧化可损害其生物学功能，导致细胞内稳态的改变。甲硫氨酸是最容易被几乎所有形式的活性氧氧化的氨基酸之一，从而产生S和R非对映异构体形式的甲硫氨酸亚砜。这些修饰可分别通过肽甲硫氨酸亚砜还原酶A和B酶（MsrA和MsrB）特异性修复。MsrA已经在从原核生物到真核生物的几种生物中检测到。MsrA与抗氧化应激和蛋白质维持密切相关，这在衰老过程中至关重要。一些研究表明，MsrA的过表达导致对氧化应激的抗性增加，而MsrA无效突变体对氧化应激更敏感。由于氧化损伤是衰老的一个关键因素，在一些生物体中MsrA的过度表达导致寿命延长，而基因的缺失则导致相反的结果。MsrA还可以通过调节靶蛋白的功能和/或表达参与ROS介导的信号转导。事实上，当MsrA过表达时，已经观察到基因表达的变化，包括某些氧化应激反应基因。这篇综述阐述了目前的知识中的含义Msr系统在保护氧化应激和衰老。
Proteins are subject to modification by reactive oxygen species (ROS), and oxidation of specific amino acid residues can impair their biological function, leading to an alteration in cellular homeostasis. Methionine is among the amino acids the most susceptible to oxidation by almost all forms of ROS, resulting in both S and R diasteroisomeric forms of methionine sulfoxide. These modifications can be repaired specifically by the peptide methionine sulfoxide reductase A and B enzymes (MsrA and MsrB), respectively. MsrA has been detected in several organisms going from prokaryotes to eukaryotes. MsrA is tightly implicated in protection against oxidative stress and in protein maintenance, which is critical in the aging process. Several studies have shown that overexpression of MsrA led to an increased resistance against oxidative stress, while MsrA null mutants are more sensitive toward oxidative stress. Since oxidative damage is a key factor in aging, overexpression of MsrA in some organisms led to an increased life span whereas deletion of the gene led to the opposite. MsrA could also be involved, by regulating the function and/or expression of target proteins, in ROS-mediated signal transduction. In fact, changes in gene expression, including certain oxidative stress-response genes, have been observed when MsrA is overexpressed. This review elaborates on the current knowledge in the implication of the Msr system in protection against oxidative stress and aging.