Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line.

Abstract:

:Membrane potential (Vmem) is a key bioelectric property of non-excitable cells that plays important roles in regulating cell proliferation. However, the regulation of Vmem 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 Vmem 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 Vmem 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Zhu L,Yu XJ,Xing S,Jin F,Yang WJ

doi

10.1038/s41598-018-24460-6

subject

Has Abstract

pub_date

2018-04-16 00:00:00

pages

6028

issue

1

issn

2045-2322

pii

10.1038/s41598-018-24460-6

journal_volume

8

pub_type

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