Yoon Miyoung, Madden Michael C, Barton Hugh A
National Research Council Research Associateship Program, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill North Carolina 27599-7315, USA.
Toxicol Sci. 2006 Feb;89(2):386-98. doi: 10.1093/toxsci/kfj045. Epub 2005 Nov 16.
Metabolism is one of the major determinants for age-related changes in susceptibility to chemicals. Aldehydes are highly reactive molecules present in the environment that also can be produced during biotransformation of xenobiotics and endogenous metabolism. Although the lung is a major target for aldehyde toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been poorly studied. The expression of ALDH in liver and lung across ages (postnatal day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity was the highest contributor in lung. Total aldehyde oxidation capability in liver increases with age, but stays constant in lung. These overall developmental profiles of ALDH expression in a tissue appear to be determined by the different composition of ALDH isoforms within the tissue and their independent temporal and tissue-specific development. ALDH2 showed the most notable tissue-specific development. Hepatic ALDH2 was increased with age, while the pulmonary form did not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased thereafter both in liver and lung. ALDH3 increased with age in liver and lung, although ALDH3A1 was only detectible in lung. Collectively, the present study indicates that, in the case of aldehyde exposure, the in vivo responses would be tissue and age dependent.
代谢是化学物质易感性与年龄相关变化的主要决定因素之一。醛类是环境中存在的高反应性分子,也可在异源生物和内源性代谢的生物转化过程中产生。尽管肺是醛类毒性的主要靶器官,但肺中醛脱氢酶(ALDHs)的早期发育研究较少。在Wistar-Han大鼠中研究了不同年龄(出生后第1、8、22和60天)肝脏和肺中ALDH的表达。在成年大鼠中,大部分肝脏ALDH活性存在于线粒体中,而胞质ALDH活性是肺中活性的最大贡献者。肝脏中的总醛氧化能力随年龄增长而增加,但在肺中保持恒定。组织中ALDH表达的这些总体发育特征似乎由组织内ALDH同工型的不同组成及其独立的时间和组织特异性发育决定。ALDH2表现出最显著的组织特异性发育。肝脏中的ALDH2随年龄增加,而肺中的ALDH2则没有。ALDH1在出生后第1天(PND1)达到最大值,此后在肝脏和肺中均下降。肝脏和肺中的ALDH3随年龄增加,尽管ALDH3A1仅在肺中可检测到。总体而言,本研究表明,在接触醛类的情况下,体内反应将取决于组织和年龄。