Cargando…
Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line
Membrane potential (V(mem)) is a key bioelectric property of non-excitable cells that plays important roles in regulating cell proliferation. However, the regulation of V(mem) itself remains largely unexplored. We found that, under nutrient starvation, during which cell division is inhibited, MKN45...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902619/ https://www.ncbi.nlm.nih.gov/pubmed/29662080 http://dx.doi.org/10.1038/s41598-018-24460-6 |
_version_ | 1783314790519668736 |
---|---|
author | Zhu, Lin Yu, Xiao-jian Xing, Sheng Jin, Feng Yang, Wei-Jun |
author_facet | Zhu, Lin Yu, Xiao-jian Xing, Sheng Jin, Feng Yang, Wei-Jun |
author_sort | Zhu, Lin |
collection | PubMed |
description | Membrane potential (V(mem)) is a key bioelectric property of non-excitable cells that plays important roles in regulating cell proliferation. However, the regulation of V(mem) itself remains largely unexplored. We found that, under nutrient starvation, during which cell division is inhibited, MKN45 gastric cancer cells were in a hyperpolarized state associated with a high intracellular chloride concentration. AMP-activated protein kinase (AMPK) activity increased, and expression of cystic fibrosis transmembrane conductance regulator (CFTR) decreased, in nutrient-starved cells. Furthermore, the increase in intracellular chloride concentration level and V(mem) hyperpolarization in nutrient-starved cells was suppressed by inhibition of AMPK activity. Intracellular chloride concentrations and hyperpolarization increased after over-activation of AMPK using the specific activator AICAR or suppression of CFTR activity using specific inhibitor GlyH-101. Under these conditions, proliferation of MKN45 cells was inhibited. These results reveal that AMPK controls the dynamic change in V(mem) by regulating CFTR and influencing the intracellular chloride concentration, which in turn influences cell-cycle progression. These findings offer new insights into the mechanisms underlying cell-cycle arrest regulated by AMPK and CFTR. |
format | Online Article Text |
id | pubmed-5902619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59026192018-04-25 Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line Zhu, Lin Yu, Xiao-jian Xing, Sheng Jin, Feng Yang, Wei-Jun Sci Rep Article Membrane potential (V(mem)) is a key bioelectric property of non-excitable cells that plays important roles in regulating cell proliferation. However, the regulation of V(mem) itself remains largely unexplored. We found that, under nutrient starvation, during which cell division is inhibited, MKN45 gastric cancer cells were in a hyperpolarized state associated with a high intracellular chloride concentration. AMP-activated protein kinase (AMPK) activity increased, and expression of cystic fibrosis transmembrane conductance regulator (CFTR) decreased, in nutrient-starved cells. Furthermore, the increase in intracellular chloride concentration level and V(mem) hyperpolarization in nutrient-starved cells was suppressed by inhibition of AMPK activity. Intracellular chloride concentrations and hyperpolarization increased after over-activation of AMPK using the specific activator AICAR or suppression of CFTR activity using specific inhibitor GlyH-101. Under these conditions, proliferation of MKN45 cells was inhibited. These results reveal that AMPK controls the dynamic change in V(mem) by regulating CFTR and influencing the intracellular chloride concentration, which in turn influences cell-cycle progression. These findings offer new insights into the mechanisms underlying cell-cycle arrest regulated by AMPK and CFTR. Nature Publishing Group UK 2018-04-16 /pmc/articles/PMC5902619/ /pubmed/29662080 http://dx.doi.org/10.1038/s41598-018-24460-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhu, Lin Yu, Xiao-jian Xing, Sheng Jin, Feng Yang, Wei-Jun Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title | Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title_full | Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title_fullStr | Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title_full_unstemmed | Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title_short | Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line |
title_sort | involvement of amp-activated protein kinase (ampk) in regulation of cell membrane potential in a gastric cancer cell line |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902619/ https://www.ncbi.nlm.nih.gov/pubmed/29662080 http://dx.doi.org/10.1038/s41598-018-24460-6 |
work_keys_str_mv | AT zhulin involvementofampactivatedproteinkinaseampkinregulationofcellmembranepotentialinagastriccancercellline AT yuxiaojian involvementofampactivatedproteinkinaseampkinregulationofcellmembranepotentialinagastriccancercellline AT xingsheng involvementofampactivatedproteinkinaseampkinregulationofcellmembranepotentialinagastriccancercellline AT jinfeng involvementofampactivatedproteinkinaseampkinregulationofcellmembranepotentialinagastriccancercellline AT yangweijun involvementofampactivatedproteinkinaseampkinregulationofcellmembranepotentialinagastriccancercellline |