Aminooxyacetic acid up-regulates the Cry1 and Bmal1 clock gene in a sirtuin 1 dependent manner. In vitro study

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-04-08 DOI:10.1016/j.taap.2025.117338

Maria Romerowicz-Misielak , Katarzyna Kozioł , Sławomir Nowak , Renata Wojnarowska-Nowak , Klaudia Łuc

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引用次数: 0

Abstract

The regulation of the cyclic oscillation of the components of the circadian clock is complex in itself. Numerous clock interactions with processes and molecules present in cells further complicate this mechanism. Recently, the anti-aging protein Silencing Information Regulator Two family member, SIRT1, has been linked with the molecular circadian clock. In this study, we investigated the in vitro effect of aminooxyacetic acid on SIRT1 expression in relation to circadian dynamics of Cry1 and Bma11 expressions in serum shocked NIH-3 T3 and HaCaT cells. The study was carried out in the context of the inhibitory activity of aminooxyacetic acid against cystathionine-β-synthase and cystathionine-γ-lyase. We have shown that aminooxyacetic acid effectively inhibits SIRT1 transcription and synthesis, which, given the pleiotropic effects of sirtuin 1 on numerous metabolic pathways, may have other implications. We also found that AOAA contributes to up-regulation of the expression of the Cry1 and Bmal1 genes in cells. This effect does not appear to be related to inhibition of the activity of cystathionine-β-synthase and cystathionine-γ-lyase. At the same time, this does not deny the role of hydrogen sulphide, a product of the activity of these enzymes, in the regulation of the circadian clock.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.