Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1α genes.
Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1α genes.
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DOI：
10.1016/j.ejphar.2012.11.051
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发表时间：
2013-01-15
影响因子：
5
通讯作者：
Parthasarathy, Sampath
中科院分区：
文献类型：
--
作者：
Kamble, Pratibha;Selvarajan, Krithika;Narasimhulu, Chandrakala Aluganti;Nandave, Mukesh;Parthasarathy, Sampath
根据乙酰水杨酸(ASA，阿司匹林)快速水解为水杨酸(SA)的能力，SA生成二羟基苯甲酸(DBA)的能力，以及后者的氧化还原反应生成过氧化氢(H_2O_2)，我们预测ASA可能具有诱导Sirtuin1(Sirt1)及其下游效应的潜力。我们观察到AsA处理肝细胞可诱导Sirt1、PgC-1α和NAD(P)H-Quone氧化还原酶1(α)基因的表达。对氧磷酶1(PON1)和芳香烃受体(AhR)siRNA的导入抑制了AsA诱导的基因表达，提示需要乙酰酯的水解和羟化生成DHBA。后者也诱导了Sirt1，证实了所提出的途径。正如预测的那样，ASA和SA处理导致了H_2O_2的产生，H_2O_2是Sirt1的已知诱导剂，目前的研究证实了这一点。更重要的是，通过追踪染料可以看出，AsA处理导致线粒体增加。我们认为，AsA通过NQO1介导的氧化/还原反应产生的DHBA可能参与了和H_2O_2的产生。由于Sirt1和PGC-1α深刻影响线粒体代谢和能量利用，AsA可能具有超越其抑制环氧合酶能力的治疗潜力。
Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter’s redox reactions to yield hydrogen peroxide (H2O2), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H2O2, a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of and H2O2. As Sirt1 and PGC-1α profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases.
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DOI：
10.1006/bbrc.1994.1368
发表时间：
1994-03-30
影响因子：
3.1
作者：
RADONS, J;HELLER, B;KOLB, H
通讯作者：
KOLB, H
DOI：
10.1073/pnas.77.9.5216
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BENSON, AM;HUNKELER, MJ;TALALAY, P
通讯作者：
TALALAY, P
影响因子：
64.8
作者：
Rodgers, JT;Lerin, C;Puigserver, P
通讯作者：
Puigserver, P
影响因子：
4.8
作者：
Nemoto, S;Fergusson, MM;Finkel, T
通讯作者：
Finkel, T
影响因子：
2.9
作者：
Smith BC;Hallows WC;Denu JM
通讯作者：
Denu JM