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The role of tumour suppressor PDCD4 in beta cell death in hypoxia
OBJECTIVE: Hypoxia is known to induce pancreatic beta cell dysfunction and apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have previously been linked with beta cell neogenesis and function. Our aim was to investigate the effects of hypoxia on cell viability, PDCD4 expression a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531437/ https://www.ncbi.nlm.nih.gov/pubmed/28750063 http://dx.doi.org/10.1371/journal.pone.0181235 |
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author | Kumar, Sandeep Marriott, Claire E. Alhasawi, Nouf F. Bone, Adrian J. Macfarlane, Wendy M. |
author_facet | Kumar, Sandeep Marriott, Claire E. Alhasawi, Nouf F. Bone, Adrian J. Macfarlane, Wendy M. |
author_sort | Kumar, Sandeep |
collection | PubMed |
description | OBJECTIVE: Hypoxia is known to induce pancreatic beta cell dysfunction and apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have previously been linked with beta cell neogenesis and function. Our aim was to investigate the effects of hypoxia on cell viability, PDCD4 expression and subcellular localisation. METHODS: MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O(2) (normoxia) for 12 or 24 hours. MTT assay, HPI staining, scanning electron microscopy, western blotting and immunocytochemistry analyses were performed to determine the effect of hypoxia on cell viability, morphology and PDCD4 expression. RESULTS: 24 hour exposure to hypoxia resulted in ~70% loss of beta cell viability (P<0.001) compared to normoxia. Both HPI staining and SEM analysis demonstrated beta cell apoptosis and necrosis after 12 hours exposure to hypoxia. ARIP cells also displayed hypoxia-induced apoptosis and altered surface morphology after 24 hours, but no significant growth difference (p>0.05) was observed between hypoxic and normoxic conditions. Significantly higher expression of PDCD4 was observed in both beta cells (P<0.001) and ductal (P<0.01) cells under hypoxic conditions compared to controls. PDCD4 expression was localised to the cytoplasm of both beta cells and ductal cells, with no observed effects of hypoxia, normoxia or serum free conditions on intracellular shuttling of PDCD4. CONCLUSION: These findings indicate that hypoxia-induced expression of PDCD4 is associated with increased beta cell death and suggests that PDCD4 may be an important factor in regulating beta cell survival during hypoxic stress. |
format | Online Article Text |
id | pubmed-5531437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55314372017-08-07 The role of tumour suppressor PDCD4 in beta cell death in hypoxia Kumar, Sandeep Marriott, Claire E. Alhasawi, Nouf F. Bone, Adrian J. Macfarlane, Wendy M. PLoS One Research Article OBJECTIVE: Hypoxia is known to induce pancreatic beta cell dysfunction and apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have previously been linked with beta cell neogenesis and function. Our aim was to investigate the effects of hypoxia on cell viability, PDCD4 expression and subcellular localisation. METHODS: MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O(2) (normoxia) for 12 or 24 hours. MTT assay, HPI staining, scanning electron microscopy, western blotting and immunocytochemistry analyses were performed to determine the effect of hypoxia on cell viability, morphology and PDCD4 expression. RESULTS: 24 hour exposure to hypoxia resulted in ~70% loss of beta cell viability (P<0.001) compared to normoxia. Both HPI staining and SEM analysis demonstrated beta cell apoptosis and necrosis after 12 hours exposure to hypoxia. ARIP cells also displayed hypoxia-induced apoptosis and altered surface morphology after 24 hours, but no significant growth difference (p>0.05) was observed between hypoxic and normoxic conditions. Significantly higher expression of PDCD4 was observed in both beta cells (P<0.001) and ductal (P<0.01) cells under hypoxic conditions compared to controls. PDCD4 expression was localised to the cytoplasm of both beta cells and ductal cells, with no observed effects of hypoxia, normoxia or serum free conditions on intracellular shuttling of PDCD4. CONCLUSION: These findings indicate that hypoxia-induced expression of PDCD4 is associated with increased beta cell death and suggests that PDCD4 may be an important factor in regulating beta cell survival during hypoxic stress. Public Library of Science 2017-07-27 /pmc/articles/PMC5531437/ /pubmed/28750063 http://dx.doi.org/10.1371/journal.pone.0181235 Text en © 2017 Kumar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kumar, Sandeep Marriott, Claire E. Alhasawi, Nouf F. Bone, Adrian J. Macfarlane, Wendy M. The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title_full | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title_fullStr | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title_full_unstemmed | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title_short | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
title_sort | role of tumour suppressor pdcd4 in beta cell death in hypoxia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531437/ https://www.ncbi.nlm.nih.gov/pubmed/28750063 http://dx.doi.org/10.1371/journal.pone.0181235 |
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