Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury.
Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury.
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DOI：
10.1002/prca.201600123
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Yu LR
中科院分区：
文献类型：
--
作者：
Gao Y;Cao Z;Yang X;Abdelmegeed MA;Sun J;Chen S;Beger RD;Davis K;Salminen WF;Song BJ;Mendrick DL;Yu LR
对乙酰氨基酚（APAP）过量是急性肝功能衰竭的主要原因。本研究旨在确定肝毒性相关的途径和肝损伤的潜在生物标志物。用低（100 mg/kg）和高（1250 mg/kg）剂量的APAP处理大鼠，并使用16 O/18 O标记和2D-LC-MS/MS的蛋白质组学方法分析处理后6小时和24小时的肝组织。APAP处理后，分子途径逐渐从分散和不太显著的扰动发展到更集中和显著的改变，并呈剂量和时间依赖性。血红素加氧酶1（HMOX 1）和胆绿素还原酶A（BLVRA）的不平衡表达与肝毒性相关。共有31种蛋白质的蛋白质丰度变化与肝损伤独特相关，其中观察到血浆中HMOX 1水平的急剧增加。在APAP治疗的小鼠中进一步验证了肝损伤相关的血浆HMOX 1显著升高。这项研究揭示了与APAP诱导的肝毒性相关的分子变化，并将HMOX 1确定为肝损伤的潜在血浆生物标志物。
Overdose of acetaminophen (APAP) is a major cause of acute liver failure. This study was aimed to identify pathways related to hepatotoxicity and potential biomarkers of liver injury. Rats were treated with low (100 mg/kg) and high (1250 mg/kg) doses of APAP, and liver tissues at 6 and 24 h post-treatment were analyzed using a proteomic approach of 16O/18O labeling and 2D-LC-MS/MS. Molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner upon APAP treatment. Imbalanced expression of hemeoxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Protein abundance changes of a total of 31 proteins were uniquely correlated to liver damage, among which a dramatic increase of HMOX1 levels in plasma was observed. Liver injury-associated significant elevation of plasma HMOX1 was further validated in mice treated with APAP. This study unveiled molecular changes associated with APAP-induced liver toxicity at the pathway levels and identified HMOX1 as a potential plasma biomarker of liver injury.
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影响因子：
3.9
作者：
James, LP;Mayeux, PR;Hinson, JA
通讯作者：
Hinson, JA
影响因子：
2.9
作者：
James, Laura P.;Chiew, Angela;Roberts, Dean
通讯作者：
Roberts, Dean
影响因子：
3.3
作者：
Gao Y;Gopee NV;Howard PC;Yu LR
通讯作者：
Yu LR
影响因子：
7.4
作者：
Abdelmegeed, Mohamed A.;Jang, Sehwan;Banerjee, Atrayee;Hardwick, James P.;Song, Byoung-Joon
通讯作者：
Song, Byoung-Joon
DOI：
10.1073/pnas.0904489106
发表时间：
2009-08-25
影响因子：
11.1
作者：
Clayton, T. Andrew;Baker, David;Nicholson, Jeremy K.
通讯作者：
Nicholson, Jeremy K.