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Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition
In a recent human study, we observed that amoxicillin treatment decreased HDL-C concentration. We hypothesize that antibiotics lower the transcription and secretion of ApoA-I, the responsible protein for HDL production. HepG2 and Caco-2 cells were exposed to increasing dose of amoxicillin, penicilli...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928897/ https://www.ncbi.nlm.nih.gov/pubmed/31783518 http://dx.doi.org/10.3390/ijms20235967 |
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author | Tayyeb, Jehad Z. Popeijus, Herman E. Mensink, Ronald P. Konings, Maurice C.J.M. Mulders, Kim H.R. Plat, Jogchum |
author_facet | Tayyeb, Jehad Z. Popeijus, Herman E. Mensink, Ronald P. Konings, Maurice C.J.M. Mulders, Kim H.R. Plat, Jogchum |
author_sort | Tayyeb, Jehad Z. |
collection | PubMed |
description | In a recent human study, we observed that amoxicillin treatment decreased HDL-C concentration. We hypothesize that antibiotics lower the transcription and secretion of ApoA-I, the responsible protein for HDL production. HepG2 and Caco-2 cells were exposed to increasing dose of amoxicillin, penicillin, and streptomycin. Secreted ApoA-I protein and mRNA transcripts were analyzed using ELISA and qPCR, respectively. To unravel underlying mechanisms, KEAP1, CPT1, and CHOP mRNA expressions were determined as well as PPARα transactivation. In HepG2 and Caco-2, amoxicillin decreased ApoA-I transcription and secretion. Effects on ApoA-I expression were clearly there for amoxicillin while no effects were observed for penicillin or streptomycin. KEAP1, CPT1, and CHOP mRNA expressions were reduced by amoxicillin treatments. Moreover, a significant correlation between ApoA-I and CPT1 mRNA expressions was found. Furthermore, amoxicillin lowered PPARα transactivation. All together, these data suggest that inhibited PPARα transactivation is involved in the effects of amoxicillin on ApoA-I. In conclusion, the direct effect of amoxicillin in treated HepG2 and Caco-2 cells was a lower ApoA-I secretion and transcription. Based on evaluating alterations in KEAP1, CPT1, and CHOP mRNA expressions plus PPARα transactivation, we suggest that a reduced PPARα activation is a potential mechanism behind the observed amoxicillin effects on ApoA-I expression. |
format | Online Article Text |
id | pubmed-6928897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69288972019-12-26 Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition Tayyeb, Jehad Z. Popeijus, Herman E. Mensink, Ronald P. Konings, Maurice C.J.M. Mulders, Kim H.R. Plat, Jogchum Int J Mol Sci Article In a recent human study, we observed that amoxicillin treatment decreased HDL-C concentration. We hypothesize that antibiotics lower the transcription and secretion of ApoA-I, the responsible protein for HDL production. HepG2 and Caco-2 cells were exposed to increasing dose of amoxicillin, penicillin, and streptomycin. Secreted ApoA-I protein and mRNA transcripts were analyzed using ELISA and qPCR, respectively. To unravel underlying mechanisms, KEAP1, CPT1, and CHOP mRNA expressions were determined as well as PPARα transactivation. In HepG2 and Caco-2, amoxicillin decreased ApoA-I transcription and secretion. Effects on ApoA-I expression were clearly there for amoxicillin while no effects were observed for penicillin or streptomycin. KEAP1, CPT1, and CHOP mRNA expressions were reduced by amoxicillin treatments. Moreover, a significant correlation between ApoA-I and CPT1 mRNA expressions was found. Furthermore, amoxicillin lowered PPARα transactivation. All together, these data suggest that inhibited PPARα transactivation is involved in the effects of amoxicillin on ApoA-I. In conclusion, the direct effect of amoxicillin in treated HepG2 and Caco-2 cells was a lower ApoA-I secretion and transcription. Based on evaluating alterations in KEAP1, CPT1, and CHOP mRNA expressions plus PPARα transactivation, we suggest that a reduced PPARα activation is a potential mechanism behind the observed amoxicillin effects on ApoA-I expression. MDPI 2019-11-27 /pmc/articles/PMC6928897/ /pubmed/31783518 http://dx.doi.org/10.3390/ijms20235967 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tayyeb, Jehad Z. Popeijus, Herman E. Mensink, Ronald P. Konings, Maurice C.J.M. Mulders, Kim H.R. Plat, Jogchum Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title | Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title_full | Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title_fullStr | Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title_full_unstemmed | Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title_short | Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition |
title_sort | amoxicillin modulates apoa-i transcription and secretion, predominantly via pparα transactivation inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928897/ https://www.ncbi.nlm.nih.gov/pubmed/31783518 http://dx.doi.org/10.3390/ijms20235967 |
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