ArticlebioRxiv : the preprint server for biology2024
Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
We examined the effect of alcohol consumption and smoking on the abundance of drug-metabolizing enzymes and transporters (DMET) in human liver microsomes (HLM) isolated from liver tissues of 94 donors. Global proteomics analysis was performed and DMET protein levels were analyzed in relation to alcohol consumption levels, smoking history, and sex using non-parametric tests (p-value ≤ 0.05; cutoff of 1.25-fold change, FC). The examination of the alcohol-induced changes was further enforced by correlational analysis, where we used arbitrary alcohol consumption grade (ACG) scaling from 0 to 4 to establish a set of protein markers. We elaborated a provisional index of alcohol exposure (PIAE) based on a combination of relative abundances of four proteins (ER chaperone HSPA5, protein disulfide isomerases PDIA3 and P4HB, and cocaine esterase CES2) best correlating with ACG. The PIAE index was then used to find its correlations with the abundances of DMET proteins. Our results demonstrate considerable alcohol-induced changes in composition of the pool of cytochrome P450 enzymes in HLM. We observed significantly increased abundances of CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase. In contrast, CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b
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