Aspirin may influence cellular energy status.
Aspirin may influence cellular energy status.
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DOI：
10.1016/j.ejphar.2014.12.020
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发表时间：
2015-02-15
影响因子：
5
通讯作者：
Parthasarathy, Sampath
中科院分区：
文献类型：
--
作者：
Kamble, Pratibha;Litvinov, Dmitry;Narasimhulu, Chandrakala Aluganti;Jiang, Xueting;Parthasarathy, Sampath
在我们以前的研究中，我们已经证明阿司匹林/乙酰水杨酸（阿萨）可能通过芳香烃受体（Ah受体）诱导sirtuins。诱导效应包括细胞对氧磷酶1（PON 1）活性和载脂蛋白A1（ApoA 1）基因表达的增加。正如预测的那样，阿萨和水杨酸（SA）处理导致H2 O2的产生，已知H2 O2是线粒体基因Sirt 4和Sirt 1的其他下游靶基因的诱导物。我们目前的质谱研究进一步证实了药物阿萨和SA的代谢。我们的研究表明，HepG 2细胞很容易将阿萨转化为SA，然后代谢为2，3-DHBA。用SA处理后，用芳烃受体siRNA转染的HepG 2细胞显示出不存在DHBA峰，如通过LC-MS/MS测量的。Sirt 1作用的MS研究还显示出由N-乙酰基Lε-赖氨酸形成的脱乙酰化和氯化产物在180.9 m/z处的峰。因此，Sirt 4、Nrf 2、Tfam、UCP 1、eNOS、HO 1和STAT 3基因的增加可能会深刻影响线粒体功能、胆固醇稳态和脂肪酸氧化，这表明阿萨可能不仅仅是抑制环氧合酶的能力。
In our previous findings, we have demonstrated that aspirin/acetyl salicylic acid (ASA) might induce sirtuins via aryl hydrocarbon receptor (Ah receptor). Induction effects included an increase in cellular paraoxonase 1 (PON1) activity and apolipoprotein A1 (ApoA1) gene expression. As predicted, ASA and salicylic acid (SA) treatment resulted in generation of H2O2, which is known to be an inducer of mitochondrial gene Sirt4 and other downstream target genes of Sirt1. Our current mass spectroscopic studies further confirm the metabolism of the drugs ASA and SA. Our studies show that HepG2 cells readily converted ASA to SA, which was then metabolized to 2,3-DHBA. HepG2 cells transfected with aryl hydrocarbon receptor siRNA upon treatment with SA showed the absence of a DHBA peak as measured by LC-MS/MS. MS studies for Sirt1 action also showed a peak at 180.9 m/z for the deacetylated and chlorinated product formed from N-acetyl Lε-lysine. Thus an increase in Sirt4, Nrf2, Tfam, UCP1, eNOS, HO1 and STAT3 genes could profoundly affect mitochondrial function, cholesterol homeostasis, and fatty acid oxidation, suggesting that ASA could be beneficial beyond simply its ability to inhibit cyclooxygenase.
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影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
DOI：
10.1161/01.atv.0000195793.73118.b4
发表时间：
2006-02-01
影响因子：
8.7
作者：
Gutierrez, A;Ratliff, EP;Davis, RA
通讯作者：
Davis, RA
影响因子：
3.8
作者：
Dykens, James A.;Jamieson, Joseph D.;Will, Yvonne
通讯作者：
Will, Yvonne
影响因子：
6.4
作者：
Jastroch M;Divakaruni AS;Mookerjee S;Treberg JR;Brand MD
通讯作者：
Brand MD
影响因子：
5
作者：
Kamble, Pratibha;Selvarajan, Krithika;Narasimhulu, Chandrakala Aluganti;Nandave, Mukesh;Parthasarathy, Sampath
通讯作者：
Parthasarathy, Sampath