LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine
Abstract This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and...
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2017
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oai:doaj.org-article:1d430abf4b9c43d19f4f369fe323f6c22021-12-02T12:32:53ZLC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine10.1038/s41598-017-04202-w2045-2322https://doaj.org/article/1d430abf4b9c43d19f4f369fe323f6c22017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04202-whttps://doaj.org/toc/2045-2322Abstract This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased. The turnover numbers of SULTs did not change, except for SULT1A1. A generally high degree of correlations was observed between SULT activities and protein amounts (r2 ≥ 0.59 except one), whereas a low degree of correlations was observed between SULT activities and mRNA expression levels (r2 ≤ 0.48 except one). HCC reduced the SULT activities via impaired protein amounts. LC-MS/MS quantification of SULTs is highly reliable measurement of SULT activities, and may be adopted for implementing precision medicine with respect to drugs mainly metabolized by SULTs in healthy and HCC patients.Cong XieTong-meng YanJia-mei ChenXiao-yan LiJuan ZouLi-jun ZhuLin-lin LuYing WangFu-yuan ZhouZhong-qiu LiuMing HuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Cong Xie Tong-meng Yan Jia-mei Chen Xiao-yan Li Juan Zou Li-jun Zhu Lin-lin Lu Ying Wang Fu-yuan Zhou Zhong-qiu Liu Ming Hu LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
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Abstract This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased. The turnover numbers of SULTs did not change, except for SULT1A1. A generally high degree of correlations was observed between SULT activities and protein amounts (r2 ≥ 0.59 except one), whereas a low degree of correlations was observed between SULT activities and mRNA expression levels (r2 ≤ 0.48 except one). HCC reduced the SULT activities via impaired protein amounts. LC-MS/MS quantification of SULTs is highly reliable measurement of SULT activities, and may be adopted for implementing precision medicine with respect to drugs mainly metabolized by SULTs in healthy and HCC patients. |
format |
article |
author |
Cong Xie Tong-meng Yan Jia-mei Chen Xiao-yan Li Juan Zou Li-jun Zhu Lin-lin Lu Ying Wang Fu-yuan Zhou Zhong-qiu Liu Ming Hu |
author_facet |
Cong Xie Tong-meng Yan Jia-mei Chen Xiao-yan Li Juan Zou Li-jun Zhu Lin-lin Lu Ying Wang Fu-yuan Zhou Zhong-qiu Liu Ming Hu |
author_sort |
Cong Xie |
title |
LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
title_short |
LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
title_full |
LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
title_fullStr |
LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
title_full_unstemmed |
LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine |
title_sort |
lc-ms/ms quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver sult activities: implication in precision medicine |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/1d430abf4b9c43d19f4f369fe323f6c2 |
work_keys_str_mv |
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