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 Repjournal_title
Scientific reportsauthors
Zhu L,Yu XJ,Xing S,Jin F,Yang WJdoi
10.1038/s41598-018-24460-6subject
Has Abstractpub_date
2018-04-16 00:00:00pages
6028issue
1issn
2045-2322pii
10.1038/s41598-018-24460-6journal_volume
8pub_type
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