Protein oxidation implicated as the primary determinant of bacterial radioresistance.
Protein oxidation implicated as the primary determinant of bacterial radioresistance.
复制标题
DOI：
10.1371/journal.pbio.0050092
复制
发表时间：
2007-04
期刊：
影响因子：
9.8
通讯作者：
Fredrickson JK
中科院分区：
文献类型：
--
作者：
Daly MJ;Gaidamakova EK;Matrosova VY;Vasilenko A;Zhai M;Leapman RD;Lai B;Ravel B;Li SM;Kemner KM;Fredrickson JK
在电离辐射（IR）损伤的细胞靶点层次中，经典的辐射毒性模型将DNA置于顶部。然而，许多原核生物被杀死的剂量的红外线，造成很少的DNA损伤。在这里，我们已经探讨了锰促进IR抗性的耐辐射异常球菌，连同其他极端IR抗性细菌具有高的细胞内Mn/Fe浓度比相比，IR敏感的细菌的性质。对于在体外和体内照射，我们证明了锰（II）离子和保护蛋白质的氧化修饰，引入羰基之间的机械联系。抑制Mn积累或Mn氧化还原循环的条件使D.对辐射敏感并且对蛋白质氧化高度敏感。X射线荧光微探针分析表明，Mn在D.抗辐射的，但铁是隔离在一个区域之间的分裂细胞。对于一组遗传多样的IR抗性和IR敏感的野生型细菌，我们的研究结果支持了这样的想法，即抗性的程度是由辐射过程中引起的氧化蛋白质损伤的水平决定的。我们提出的情况下，蛋白质，而不是DNA，是IR在敏感细菌的生物作用的主要目标，和极端的耐锰积累细菌是基于蛋白质的保护。放射生物学的一个最初目标是解释为什么细胞对电离辐射（IR）如此敏感。早期对细菌的研究将DNA作为主要的辐射敏感靶点，这一论断仍然是现代辐射毒性模型的核心。最近，重点已经转移到理解为什么细菌，如耐辐射异常球菌是非常耐IR，通过专注于DNA修复系统在恢复过程中表示从高剂量的IR。不幸的是，作为DNA为中心的假设的关键特征的极端电阻已经变得越来越弱，替代细胞目标的研究已经远远落后，主要是因为它们的相对生物复杂性。最近的研究表明，极端水平的细菌IR抗性与高细胞内Mn（II）浓度相关，抗性和敏感细菌同样容易受到IR诱导的DNA损伤。目前的工作建立了Mn（II）和保护蛋白质免受辐射损伤之间的机制联系。与耐药细菌相反，天然敏感细菌对IR诱导的蛋白质氧化高度敏感。我们提出，敏感细菌在辐射剂量下维持致命水平的蛋白质损伤，引起相对较小的DNA损伤，并且细菌的极端抗性依赖于蛋白质保护。耐辐射奇球菌细胞内高浓度的锰可保护蛋白质而非DNA免受电离辐射诱导的氧化损伤。蛋白质保护可能对这些细菌的已知辐射抗性至关重要。
In the hierarchy of cellular targets damaged by ionizing radiation (IR), classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria. For in vitro and in vivo irradiation, we demonstrate a mechanistic link between Mn(II) ions and protection of proteins from oxidative modifications that introduce carbonyl groups. Conditions that inhibited Mn accumulation or Mn redox cycling rendered D. radiodurans radiation sensitive and highly susceptible to protein oxidation. X-ray fluorescence microprobe analysis showed that Mn is globally distributed in D. radiodurans, but Fe is sequestered in a region between dividing cells. For a group of phylogenetically diverse IR-resistant and IR-sensitive wild-type bacteria, our findings support the idea that the degree of resistance is determined by the level of oxidative protein damage caused during irradiation. We present the case that protein, rather than DNA, is the principal target of the biological action of IR in sensitive bacteria, and extreme resistance in Mn-accumulating bacteria is based on protein protection. One original goal of radiobiology was to explain why cells are so sensitive to ionizing radiation (IR). Early studies in bacteria incriminated DNA as the principal radiosensitive target, an assertion that remains central to modern radiation toxicity models. More recently, the emphasis has shifted to understanding why bacteria such as Deinococcus radiodurans are extremely resistant to IR, by focusing on DNA repair systems expressed during recovery from high doses of IR. Unfortunately, as key features of DNA-centric hypotheses of extreme resistance have grown weaker, the study of alternative cellular targets has lagged far behind, mostly because of their relative biological complexity. Recent studies have shown that extreme levels of bacterial IR resistance correlate with high intracellular Mn(II) concentrations, and resistant and sensitive bacteria are equally susceptible to IR-induced DNA damage. The current work establishes a mechanistic link between Mn(II) and protection of proteins from radiation damage. In contrast to resistant bacteria, naturally sensitive bacteria are highly susceptible to IR-induced protein oxidation. We propose that sensitive bacteria sustain lethal levels of protein damage at radiation doses that elicit relatively little DNA damage, and that extreme resistance in bacteria is dependent on protein protection. A high intracellular concentration of manganese inDeinococcus radiodurans protects proteins, but not DNA, from ionizing radiation-induced oxidative damage. Protein protection may be critical to the known radiation resistance of these bacteria.
登录
查看更多内容
影响因子：
2.6
作者：
Kranner, I;Birtic, S
通讯作者：
Birtic, S
影响因子：
3.2
作者：
Eltsov, M;Dubochet, J
通讯作者：
Dubochet, J
影响因子：
3.1
作者：
Gérard, E;Jolivet, E;Forterre, P
通讯作者：
Forterre, P
影响因子：
56.9
作者：
Kemner, KM;Kelly, SD;Nealson, KH
通讯作者：
Nealson, KH
影响因子：
3.2
作者：
DALY, MJ;MINTON, KW
通讯作者：
MINTON, KW