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Exposure of colonic epithelial cells to oxidative and endoplasmic reticulum stress causes rapid potassium efflux and calcium influx

journal contribution
posted on 2023-05-17, 15:17 authored by Svetlana ShabalaSvetlana Shabala, Walker, EJ, Eklund, A, Randall-Demllo, S, Sergey ShabalaSergey Shabala, Nuri GuvenNuri Guven, Anthony CookAnthony Cook, Rajaraman Eri
Endoplasmic reticulum (ER) stress and oxidative stress have recently been linked to the pathogenesis of inflammatory bowel diseases. Under physiological conditions, intestinal epithelial cells are exposed to ER and oxidative stress affecting the cellular ionic homeostasis. However, these altered ion flux 'signatures' during these stress conditions are poorly characterized. We investigated the kinetics of K+, Ca2+ and H+ ion fluxes during ER and oxidative stress in a colonic epithelial cell line LS174T using a non-invasive microelectrode ion flux estimation technique. ER and oxidative stress were induced by cell exposure to tunicamycin (TM) and copper ascorbate (CuAsc), respectively, from 1 to 24 h. Dramatic K+ efflux was observed following acute ER stress with peak K+ efflux being -30.6 and -138.7 nmolm-2s-1 for 10 and 50ugml-1, respectively (p<0.01). TM-dependent Ca2+ uptake was more prolonged with peak values of 0.85 and 2.68 nmolm-2s-1 for 10 and 50 mgml-1 TM, respectively (p<0.02). Ion homeostasis was also affected by the duration of ER stress. Increased duration of TM treatment from 0 to 18 h led to increases in both K+ efflux and Ca2+ uptake. While K+ changes were significantly higher at each time point tested, Ca2+ uptake was significantly higher only after prolonged treatment (18 h). CuAsc also led to an increased K+ efflux and Ca2+ uptake. Functional assays to investigate the effect of inhibiting K+ efflux with tetraethylammonium resulted in increased cell viability. We conclude that ER/oxidative stress in colonic epithelial cells cause dramatic K+, Ca2+ and H+ ion flux changes, which may predispose this lineage to poor stress recovery reminiscent of that seen in inflammatory bowel diseases.

History

Publication title

Cell Biochemistry and Function

Volume

31

Issue

7

Pagination

603-611

ISSN

1099-0844

Department/School

Tasmanian Institute of Agriculture (TIA)

Publisher

John Wiley & Sons Ltd.

Place of publication

The Atrium, Chichester, West Sussex PO19 8SQ, UK

Rights statement

Copyright 2012 John Wiley & Sons, Ltd.

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the health sciences

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