Urinary 8-hydroxyguanine may be a better marker of oxidative stress than 8-hydroxydeoxyguanosine in relation to the life spans of various species

Urinary 8-hydroxyguanine may be a better marker of oxidative stress than 8-hydroxydeoxyguanosine in relation to the life spans of various species
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DOI:
10.1089/ars.2006.8.985
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发表时间:
2006-05-01
影响因子:
6.6
通讯作者:
Kasai, Hiroshi
Kasai, Hiroshi
中科院分区:
生物学2区
文献类型:
--
作者:
Svoboda, Peter;Maekawa, Muneyuki;Kasai, Hiroshi

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氧化性DNA损伤被认为与衰老过程有关。与长寿物种相比,潜在寿命较短的物种通常具有较高的比代谢率(SMR),预计氧化应激和DNA损伤水平会增加。使用基于电化学检测的自动化HPLC方法测量不同潜在寿命的哺乳动物(小鼠、大鼠、豚鼠、猫、黑猩猩和人)尿样中氧化DNA损伤标志物8-羟基脱氧鸟苷(8-OH-dG)和8-羟基鸟嘌呤(8-OH-Gua)的水平。物种的潜在寿命(对数转换)与尿中8-OH-dG水平(8-OH-dG/肌酐)之间没有显著的线性相关性(r =-0.71,p = 0.11),尽管具有较长寿命的物种,如黑猩猩和人类,检测到的水平最低。相比之下,物种的潜在寿命(对数转换)和尿中8-OH-胍水平(8-OH-胍/肌酐)之间的负线性相关性是显著的(r =-0.97,p = 0.002)。SMR与8-OH-dG/肌酐(r = 0.91,p = 0.01)和8-OH-Gua/肌酐(r = 0.90,p = 0.01)呈线性正相关。这些结果表明,8-OH-Gua,而不是8-OH-dG,可能是氧化损伤的更一般的标志物。
Oxidative DNA damage is believed to be involved in the aging process. Species with shorter potential life spans generally have a higher specific metabolic rate (SMR), and would be expected to have increased levels of oxidative stress and DNA damage, as compared to long-lived species. An automatized HPLC method based on electrochemical detection was used to measure the levels of the oxidative DNA damage markers 8-hydroxydeoxyguanosine (8-OH-dG) and 8-hydroxyguanine (8-OH-Gua) in urinary samples from mammals with various potential life spans (mice, rats, guinea pigs, cats, chimpanzees, and humans). There was no significant linear correlation (r = -0.71,p = 0.11) between the species' potential life spans (log transformed) and the urinary levels of 8-OH-dG as normalized to creatinine (8-OH-dG/creatinine), although the species with longer life spans, such as chimpanzee and human, had among the lowest levels detected. In contrast, the negative linear correlation between the species' potential life span (log transformed) and the urinary levels of 8-OH-Gua as normalized to creatinine (8-OH-Gua/creatinine), was significant (r = -0.97, p = 0.002). In addition, there was a positive linear and significant correlation between SMR and 8-OH-dG/creatinine (r = 0.91, p = 0.01) or 8-OH-Gua/creatinine (r = 0.90,p = 0.01). These results suggest that 8-OH-Gua, rather than 8-OH-dG, may be a more general marker for oxidative damage.