ArticlePloS one2012
Zinc sensing receptor signaling, mediated by GPR39, reduces butyrate-induced cell death in HT29 colonocytes via upregulation of clusterin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39.CNS neuroscience & therapeutics · 2023Review
- Functions of the Zinc-Sensing Receptor GPR39 in Regulating Intestinal Health in Animals.International journal of molecular sciences · 2022Review
- The expression and clinical significance of GPR39 in colon cancer.Irish journal of medical science · 2022Article
- Clonal cytopenia of undetermined significance and atypical Behçet's: the importance of zinc.BMJ case reports · 2022Article
- Zinc Signaling in the Mammary Gland: For Better and for Worse.Biomedicines · 2021Review
- Role of GPR39 in Neurovascular Homeostasis and Disease.International journal of molecular sciences · 2021Review
- The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.International journal of molecular sciences · 2021Review
- Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells.Frontiers in cellular neuroscience · 2021Review
- microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC.Journal of cellular and molecular medicine · 2019Article
- Role of ion channels in gastrointestinal cancer.World journal of gastroenterology · 2019Review
- Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth.Scientific reports · 2018Article
- The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease.International journal of molecular sciences · 2018Review
- Solute carrier transporters: potential targets for digestive system neoplasms.Cancer management and research · 2018Review
- Obestatin controls skeletal muscle fiber-type determination.Scientific reports · 2017Article
- The ZnBiochimica et biophysica acta. Molecular basis of disease · 2017Article
- Discovery and Characterization of Novel GPR39 Agonists Allosterically Modulated by Zinc.Molecular pharmacology · 2016Article
- The zinc sensing receptor, ZnR/GPR39, triggers metabotropic calcium signalling in colonocytes and regulates occludin recovery in experimental colitis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Article
- Zn(2+) at a cellular crossroads.Current opinion in chemical biology · 2016Review
- The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon.Cell death & disease · 2014Article
- Clusterin: a key player in cancer chemoresistance and its inhibition.OncoTargets and therapy · 2014Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc enhances epithelial proliferation, protects the digestive epithelial layer and has profound antiulcerative and antidiarrheal roles in the colon. Despite the clinical significance of this ion, the mechanisms linking zinc to these cellular processes are poorly understood. We have previously identified an extracellular Zn(2+) sensing G-protein coupled receptor (ZnR) that activates Ca(2+) signaling in colonocytes, but its molecular identity as well as its effects on colonocytes' survival remained elusive. Here, we show that Zn(2+), by activation of the ZnR, protects HT29 colonocytes from butyrate induced cell death. Silencing of the G-protein coupled receptor GPR39 expression abolished ZnR-dependent Ca(2+) release and Zn(2+)-dependent survival of butyrate-treated colonocytes. Importantly, GPR39 also mediated ZnR-dependent upregulation of Na(+)/H(+) exchange activity as this activity was found in native colon tissue but not in tissue obtained from GPR39 knock-out mice. Although ZnR-dependent upregulation of Na(+)/H(+) exchange reduced the cellular acid load induced by butyrate, it did not rescue HT29 cells from butyrate induced cell death. ZnR/GPR39 activation however, increased the expression of the anti-apoptotic protein clusterin in butyrate-treated cells. Furthermore, silencing of clusterin abolished the Zn(2+)-dependent survival of HT29 cells. Altogether, our results demonstrate that extracellular Zn(2+), acting through ZnR, regulates intracellular pH and clusterin expression thereby enhancing survival of HT29 colonocytes. Moreover, we identify GPR39 as the molecular moiety of ZnR in HT29 and native colonocytes.
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