Asp-Ala-His-Lys (DAHK) Inhibits Copper-Induced Oxidative DNA Double Strand Breaks and Telomere Shortening

doi:10.1006/bbrc.2001.4533

Biochemical and Biophysical Research Communications

Volume 282, Issue 1, 23 March 2001, Pages 356-360

https://doi.org/10.1006/bbrc.2001.4533 Get rights and content

Abstract

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-DAHK:Cu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHK:Cu), 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-DAHK:Cu). 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.

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^☆: Abbreviations used: DAHK, Asp-Ala-His-Lys; ROS, reactive oxygen species; OH^•, hydroxyl radical; H₂O₂, hydrogen peroxide; O^•−₂, superoxide; Cu, copper; Fe, iron; PBS, phosphate buffered saline; IMDM, Iscove's modified Dulbecco's media; FCS, fetal calf serum; TAE, Tris acetic acid EDTA; DIG, digoxigenin; 8-oxo-dG, 8-oxo-deoxyguanosine.

¹: To whom correspondence should be addressed. Fax: 303-789-0510. E-mail: [email protected].

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Regular ArticleAsp-Ala-His-Lys (DAHK) Inhibits Copper-Induced Oxidative DNA Double Strand Breaks and Telomere Shortening☆

Abstract

Biochim. Biophys. Acta

Mutat. Res.

Free Radic. Biol. Med.

Biochem. Biophys. Res. Commun.

J. Theor. Biol.

Exp. Cell Res.

J. Emerg. Med.

J. Biol. Chem.

J. Biol. Chem.

Free Radic. Biol. Med.

Biochim. Biophys. Acta

Arch. Biochem. Biophys.

Free Radic. Biol. Med.

FEBS Lett.

J. Mol. Cell Cardiol.

The role of 8-hydroxyguanine in carcinogenesis

Carcinogenesis

Oxygen-derived free radicals in postischemic tissue injury

N. Engl. J. Med.

Regular Article
Asp-Ala-His-Lys (DAHK) Inhibits Copper-Induced Oxidative DNA Double Strand Breaks and Telomere Shortening☆