On January 29, 2019, Ohtsuki, Yuya; Sanoh, Seigo; Santoh, Masataka; Ejiri, Yoko; Ohta, Shigeru; Kotake, Yaichiro published an article.SDS of cas: 118-55-8 The title of the article was Inhibition of cytochrome P450 3A protein degradation and subsequent increase in enzymatic activity through p38 MAPK activation by acetaminophen and salicylate derivatives. And the article contained the following:
We previously reported that acetaminophen (APAP) caused accumulation of functional CYP3A protein via inhibition of CYP3A protein degradation through reduction of glycoprotein 78 (gp78), an E3 ligase of the ubiquitin proteasome system. Furthermore, N-acetyl-m-aminophenol, a regioisomer of APAP causes CYP3A protein accumulation, whereas p-acetamidobezoic acid, in which a hydroxy group of APAP was substituted for a carboxy group, did not lead to the same effects. In this study, we selected 32 compounds including a phenolic hydroxyl group such as APAP and explored the compounds that increased CYP3A enzyme activity to analyze their common mechanism. Four compounds, including salicylate, increased CYP3A enzyme activity and led to the accumulation of functional CYP3A protein similarly to APAP. APAP and salicylate activate p38 mitogen-activated protein kinase (p38 MAPK). gp78 is known to be phosphorylated by p38 MAPK; so, we investigated the relationship between p38 MAPK and CYP3A. APAP activated p38 MAPK, decreased gp78 protein expression, and subsequently induced CYP3A protein expression in a time-dependent manner. When SB203580, a p38 MAPK inhibitor, was co-administered with APAP, the inhibitory effects of APAP on CYP3A protein degradation were suppressed. In this study, we demonstrated the involvement of the p38 MAPK-gp78 pathway in suppressing CYP3A protein degradation by APAP. Salicylate derivatives may also suppress the CYP3A protein degradation The experimental process involved the reaction of Phenyl Salicylate(cas: 118-55-8).SDS of cas: 118-55-8
The Article related to cytochrome protein degradation enzymic activity mapk activation acetaminophen salicylate, acetaminophen, cytochrome p450 3a, glycoprotein 78, protein degradation, salicylate, p38 mitogen-activated protein kinase and other aspects.SDS of cas: 118-55-8
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