Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid abundant in fish oil that exerts a wide spectrum of documented beneficial health effects in humans. Because dietary interventions are relatively inexpensive and are widely assumed to be safe, they have broad public appeal. Their endorsement can potentially have a major impact on human health, but hard mechanistic evidence that specifies how these derivatives work at the cellular level is limited. EPA (50 microM) caused a small elevation of cytoplasmic Ca(2+) concentration ([Ca(2+)]) in intact NCM460 human colonic epithelial cells as measured by fura 2 and a profound drop of [Ca(2+)] within the endoplasmic reticulum (ER) of permeabilized cells as monitored by compartmentalized mag-fura 2. Total internal reflection fluorescence microscopy showed that this loss of ER store [Ca(2+)] led to translocation of the ER-resident transmembrane Ca(2+) sensor STIM1. Using sensitive FRET-based sensors for cAMP in single cells, we further found that EPA caused a substantial increase in cellular cAMP concentration, a large fraction of which was dependent on the drop in ER [Ca(2+)], but independent of cytosolic Ca(2+). An additional component of the EPA-induced cAMP signal was sensitive to the phosphodiesterase inhibitor isobutyl methylxanthine. We conclude that EPA slowly releases ER Ca(2+) stores, resulting in the generation of cAMP. The elevated cAMP is apparently independent of classical G protein-coupled receptor activation and is likely the consequence of a newly described "store-operated" cAMP signaling pathway that is mediated by STIM1.

Original publication

DOI

10.1152/ajpgi.00028.2010

Type

Journal article

Journal

Am J Physiol Gastrointest Liver Physiol

Publication Date

09/2010

Volume

299

Pages

G715 - G722

Keywords

1-Methyl-3-isobutylxanthine, Calcium, Cell Line, Colon, Cyclic AMP, Eicosapentaenoic Acid, Endoplasmic Reticulum, Epithelial Cells, Humans, Inositol 1,4,5-Trisphosphate, Intestinal Mucosa, Membrane Proteins, Neoplasm Proteins, Phosphodiesterase Inhibitors, Stromal Interaction Molecule 1