دورية أكاديمية

Dynamic recycling of extracellular ATP in human epithelial intestinal cells.

التفاصيل البيبلوغرافية
العنوان: Dynamic recycling of extracellular ATP in human epithelial intestinal cells.
المؤلفون: Saffioti NA; Instituto de Química y Físico-Química Biológicas 'Prof. Alejandro C. Paladini', Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Cátedra de Química Biológica, Buenos Aires, Argentina.; Instituto de Nanosistemas, Universidad Nacional de General San Martin, Buenos Aires, Argentina., Alvarez CL; Instituto de Química y Físico-Química Biológicas 'Prof. Alejandro C. Paladini', Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.; Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Departamento de Biodiversidad y Biología Experimental, Buenos Aires, Argentina., Bazzi Z; Instituto de Química y Físico-Química Biológicas 'Prof. Alejandro C. Paladini', Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Cátedra de Química Biológica, Buenos Aires, Argentina., Gentilini MV; Fundación Favaloro Hospital Universitario, Unidad de Insuficiencia, Rehabilitación y Trasplante Intestinal, Buenos Aires, Argentina.; Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB, CONICET, Universidad Favaloro), Laboratorio de Inmunología asociada al Trasplante, Buenos Aires, Argentina., Gondolesi GE; Fundación Favaloro Hospital Universitario, Unidad de Insuficiencia, Rehabilitación y Trasplante Intestinal, Buenos Aires, Argentina.; Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB, CONICET, Universidad Favaloro), Laboratorio de Inmunología asociada al Trasplante, Buenos Aires, Argentina., Schwarzbaum PJ; Instituto de Química y Físico-Química Biológicas 'Prof. Alejandro C. Paladini', Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Cátedra de Química Biológica, Buenos Aires, Argentina., Schachter J; Instituto de Química y Físico-Química Biológicas 'Prof. Alejandro C. Paladini', Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Cátedra de Química Biológica, Buenos Aires, Argentina.
المصدر: PLoS computational biology [PLoS Comput Biol] 2023 Jun 29; Vol. 19 (6), pp. e1011196. Date of Electronic Publication: 2023 Jun 29 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2005]-
مواضيع طبية MeSH: Adenosine Triphosphate*/metabolism , Epithelial Cells*/metabolism, Humans ; Caco-2 Cells ; Phospholipid Transfer Proteins
مستخلص: Intestinal epithelial cells play important roles in the absorption of nutrients, secretion of electrolytes and food digestion. The function of these cells is strongly influenced by purinergic signalling activated by extracellular ATP (eATP) and other nucleotides. The activity of several ecto-enzymes determines the dynamic regulation of eATP. In pathological contexts, eATP may act as a danger signal controlling a variety of purinergic responses aimed at defending the organism from pathogens present in the intestinal lumen. In this study, we characterized the dynamics of eATP on polarized and non-polarized Caco-2 cells. eATP was quantified by luminometry using the luciferin-luciferase reaction. Results show that non-polarized Caco-2 cells triggered a strong but transient release of intracellular ATP after hypotonic stimuli, leading to low micromolar eATP accumulation. Subsequent eATP hydrolysis mainly determined eATP decay, though this effect could be counterbalanced by eATP synthesis by ecto-kinases kinetically characterized in this study. In polarized Caco-2 cells, eATP showed a faster turnover at the apical vs the basolateral side. To quantify the extent to which different processes contribute to eATP regulation, we created a data-driven mathematical model of the metabolism of extracellular nucleotides. Model simulations showed that eATP recycling by ecto-AK is more efficient a low micromolar eADP concentrations and is favored by the low eADPase activity of Caco-2 cells. Simulations also indicated that a transient eATP increase could be observed upon the addition of non-adenine nucleotides due the high ecto-NDPK activity in these cells. Model parameters showed that ecto-kinases are asymmetrically distributed upon polarization, with the apical side having activity levels generally greater in comparison with the basolateral side or the non-polarized cells. Finally, experiments using human intestinal epithelial cells confirmed the presence of functional ecto-kinases promoting eATP synthesis. The adaptive value of eATP regulation and purinergic signalling in the intestine is discussed.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Saffioti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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سلسلة جزيئية: figshare 10.6084/m9.figshare.21938651.v1
المشرفين على المادة: 8L70Q75FXE (Adenosine Triphosphate)
0 (Phospholipid Transfer Proteins)
تواريخ الأحداث: Date Created: 20230629 Date Completed: 20230714 Latest Revision: 20230718
رمز التحديث: 20230718
مُعرف محوري في PubMed: PMC10337955
DOI: 10.1371/journal.pcbi.1011196
PMID: 37384797
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7358
DOI:10.1371/journal.pcbi.1011196