Cobalt-mediated oxidative DNA damage and its prevention by polyphenol antioxidants

被引:6
|
作者
Angele-Martinez, Carlos [1 ]
Murray, Joseph [1 ]
Stewart, Paul A. [1 ]
Haines, Jennifer [1 ]
Gaertner, Andrea A. E. [1 ]
Brumaghim, Julia L. [1 ]
机构
[1] Clemson Univ, Dept Chem, Clemson, SC 29634 USA
基金
美国国家科学基金会;
关键词
Cobalt; DNA damage; Polyphenol; Reactive oxygen species; Hydrogen peroxide; Ascorbate; SINGLET OXYGEN PRODUCTION; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; ASCORBIC-ACID; METAL-BINDING; WHOLE-BLOOD; IRON; CLEAVAGE; STRESS; CYTOTOXICITY;
D O I
10.1016/j.jinorgbio.2022.112024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although cobalt is a required nutrient, it is toxic due to its ability to generate reactive oxygen species (ROS) and damage DNA. ROS generation by Co2+ often has been compared to that of Fe2+ or Cu+, disregarding the reduction potential differences among these metal ions. In plasmid DNA damage studies, a maximum of 15% DNA damage is observed with Co2+/H2O2 treatment (up to 50 mu M and 400 mu M, respectively) significantly lower than the 90% damage observed for Fe2+/H2O2 or Cu+/H2O2 treatment. However, when ascorbate is added to the Co2+/H2O2 system, a synergistic effect results in 90% DNA damage. DNA damage by Fe2+/H2O2 can be prevented by polyphenol antioxidants, but polyphenols both prevent and promote DNA damage by Cu+/H2O2. When tested for cobalt-mediated DNA damage affects, eight of ten polyphenols (epicatechin gallate, epigallocatechin gallate, propyl gallate, gallic acid, methyl-3,4,5-trihydroxybenzoate, methyl-4,5-dihydroxybenzoate, protocatechuic acid, and epicatechin) prevent cobalt-mediated DNA damage with IC50 values of 1.3 to 27 mu M and two (epigallocatechin and vanillic acid) prevent little to no DNA damage. EPR studies demonstrate cobalt-mediated formation of (OH)-O-center dot, O2(center dot-) and (OOH)-O-center dot, but not O-1(2) in the presence of H2O2 and ascorbate. Epigallocatechin gallate and methyl-4,5-dihydroxybenzoate significantly reduce ROS generated by Co2+/H2O2/ ascorbate, consistent with their prevention of cobalt-mediated DNA damage. Thus, while cobalt, iron, and copper are all d-block metal ions, cobalt ROS generation and its prevention is significantly different from that of iron and copper.
引用
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页数:9
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