Bar-Or D, Thomas G W, Rael L T, Lau E P, Winkler J V
Trauma Research, Swedish Medical Center, Englewood, Colorado, 80110, USA.
Biochem Biophys Res Commun. 2001 Mar 23;282(1):356-60. doi: 10.1006/bbrc.2001.4533.
Both DNA and the telomeric sequence are susceptible to copper-mediated reactive oxygen species (ROS) damage, particularly damage attributed to hydroxyl radicals. In this study, ROS-induced DNA double strand breaks and telomere shortening were produced by exposure to copper and ascorbic acid. Asp-Ala-His-Lys (DAHK), a specific copper chelating tetrapeptide d-analog of the N-terminus of human albumin, attenuated DNA strand breaks in a dose dependent manner. d-DAHK, at a ratio of 4:1 (d-DAHKCu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHKCu), completely protected DNA in Raji cells exposed to copper/ascorbate. Southern blots of DNA treated with copper/ascorbate showed severe depletion and shortening of telomeres and Raji cell treated samples showed some conservation of telomere sequences. d-DAHK provided complete telomere length protection at a ratio of 2:1 (d-DAHKCu). The human albumin N-terminus analog, d-DAHK, protects DNA and telomeres against copper-mediated ROS damage and may be a useful therapeutic adjunct in ROS disease processes.
DNA和端粒序列都易受铜介导的活性氧（ROS）损伤，尤其是由羟基自由基引起的损伤。在本研究中，通过暴露于铜和抗坏血酸产生了ROS诱导的DNA双链断裂和端粒缩短。天冬氨酸-丙氨酸-组氨酸-赖氨酸（DAHK），一种人白蛋白N端的特异性铜螯合四肽d-类似物，以剂量依赖方式减轻DNA链断裂。d-DAHK与铜的比例为4:1（d-DAHKCu）时，能完全保护分离的DNA免受双链断裂影响；比例为2:1（d-DAHKCu）时，能完全保护暴露于铜/抗坏血酸的Raji细胞中的DNA。用铜/抗坏血酸处理的DNA的Southern印迹显示端粒严重缺失和缩短，而Raji细胞处理样品显示端粒序列有一定程度的保留。d-DAHK在比例为2:1（d-DAHKCu）时能提供完全的端粒长度保护。人白蛋白N端类似物d-DAHK可保护DNA和端粒免受铜介导的ROS损伤，可能是ROS疾病过程中一种有用的治疗辅助手段。
