Chen Changbin, Dickman Martin B
Department of Plant Pathology, University of Nebraska, 406 Plant Sciences Hall, Lincoln, NE 68583-0722, USA.
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3459-64. doi: 10.1073/pnas.0407960102. Epub 2005 Feb 7.
The role of reactive oxygen species (ROS) in cell communication, control of gene expression, and oxygen sensing is well established. Inappropriate regulation of ROS levels can damage cells, resulting in a diseased state. In Colletotrichum trifolii, a fungal pathogen of alfalfa, the mutationally activated oncogenic fungal Ras (DARas) elevates levels of ROS, causing abnormal fungal growth and development and eventual apoptotic-like cell death but only when grown under nutrient-limiting conditions. Remarkably, restoration to the wild-type phenotype requires only proline. Here, we describe a generally unrecognized function of proline: its ability to function as a potent antioxidant and inhibitor of programmed cell death. Addition of proline to DARas mutant cells effectively quenched ROS levels and prevented cell death. Treating cells with inhibitors of ROS production yielded similar results. In addition, proline protected wild-type C. trifolii cells against various lethal stresses, including UV light, salt, heat, and hydrogen peroxide. These observations appear to be general because proline also protected yeast cells from lethal levels of the ROS-generating herbicide methyl viologen (paraquat), suggesting a common protective role for proline in response to oxidative stress. The ability of proline to scavenge intracellular ROS and inhibit ROS-mediated apoptosis may be an important and broad-based function of this amino acid in responding to cellular stress, in addition to its well established role as an osmolyte.
活性氧（ROS）在细胞通讯、基因表达调控及氧感知中的作用已得到充分证实。ROS水平的不当调节会损害细胞，导致疾病状态。在苜蓿的真菌病原体三叶草炭疽菌中，经突变激活的致癌真菌Ras（DARas）会提高ROS水平，导致真菌生长发育异常并最终出现类似凋亡的细胞死亡，但仅在营养限制条件下生长时才会出现这种情况。值得注意的是，恢复到野生型表型仅需要脯氨酸。在此，我们描述了脯氨酸一种普遍未被认识的功能：其作为一种有效的抗氧化剂和程序性细胞死亡抑制剂的能力。向DARas突变细胞中添加脯氨酸可有效淬灭ROS水平并防止细胞死亡。用ROS产生抑制剂处理细胞也产生了类似的结果。此外，脯氨酸保护野生型三叶草炭疽菌细胞免受各种致命胁迫，包括紫外线、盐、热和过氧化氢。这些观察结果似乎具有普遍性，因为脯氨酸也保护酵母细胞免受产生ROS的除草剂百草枯致死水平的影响，这表明脯氨酸在应对氧化应激方面具有共同的保护作用。脯氨酸清除细胞内ROS并抑制ROS介导的凋亡的能力，除了其作为渗透溶质已确立的作用外，可能是这种氨基酸在应对细胞应激时的一项重要且广泛的功能。
