Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening.
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.
Bar-Or
D
D
Trauma Research, Swedish Medical Center, Englewood, Colorado, 80110, USA. dbaror@dmibio.com
Thomas
G W
GW
Rael
L T
LT
Lau
E P
EP
Winkler
J V
JV
D002460:Cell Line; D003300:Copper / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress; D016615:Telomere / Q000187:drug effects*
D009842:Oligopeptides; D003300:Copper; D004247:DNA