The role of tumour suppressor PDCD4 in beta cell death in hypoxia
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 subcellu...
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| Veröffentlicht in: | PloS one 2017-07, Vol.12 (7), p.e0181235-e0181235 |
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| creator | Kumar, Sandeep Marriott, Claire E Alhasawi, Nouf F Bone, Adrian J Macfarlane, Wendy M |
| description | 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.
MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O2 (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.
24 hour exposure to hypoxia resulted in ~70% loss of beta cell viability (P0.05) was observed between hypoxic and normoxic conditions. Significantly higher expression of PDCD4 was observed in both beta cells (P |
| doi_str_mv | 10.1371/journal.pone.0181235 |
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MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O2 (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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0181235</identifier><identifier>PMID: 28750063</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anoxia ; Apoptosis ; Apoptosis Regulatory Proteins - metabolism ; Beta cells ; Biology and Life Sciences ; Cell Death ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Complications and side effects ; Cytology ; Cytoplasm ; Electron microscopy ; Exposure ; Gene expression ; Genetic aspects ; Hypoxia ; Immunocytochemistry ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - pathology ; Kinases ; Laboratories ; Medicine and Health Sciences ; Mice ; Mortality ; Pancreas ; Pancreatic beta cells ; Physical Sciences ; Physiological aspects ; Rats ; Research and Analysis Methods ; RNA-Binding Proteins - metabolism ; Rodents ; Scanning electron microscopy ; Staining ; Subcellular Fractions - metabolism ; Tumors ; Western blotting</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0181235-e0181235</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Kumar et al 2017 Kumar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6f1ea4318ffe791be65968616537c15edda510288411de53e96a15bc0a4658763</citedby><cites>FETCH-LOGICAL-c692t-6f1ea4318ffe791be65968616537c15edda510288411de53e96a15bc0a4658763</cites><orcidid>0000-0002-7482-8906</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531437/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531437/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2097,2916,23848,27906,27907,53773,53775,79350,79351</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28750063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Palle, Komaraiah</contributor><creatorcontrib>Kumar, Sandeep</creatorcontrib><creatorcontrib>Marriott, Claire E</creatorcontrib><creatorcontrib>Alhasawi, Nouf F</creatorcontrib><creatorcontrib>Bone, Adrian J</creatorcontrib><creatorcontrib>Macfarlane, Wendy M</creatorcontrib><title>The role of tumour suppressor PDCD4 in beta cell death in hypoxia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O2 (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.
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.
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.</description><subject>Animals</subject><subject>Anoxia</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Beta cells</subject><subject>Biology and Life Sciences</subject><subject>Cell Death</subject><subject>Cell Hypoxia</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Complications and side effects</subject><subject>Cytology</subject><subject>Cytoplasm</subject><subject>Electron microscopy</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Hypoxia</subject><subject>Immunocytochemistry</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Insulin-Secreting Cells - pathology</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mortality</subject><subject>Pancreas</subject><subject>Pancreatic beta cells</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Rats</subject><subject>Research and Analysis Methods</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Rodents</subject><subject>Scanning electron microscopy</subject><subject>Staining</subject><subject>Subcellular Fractions - metabolism</subject><subject>Tumors</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r1EAUhoMotlb_gWhAEL3Ydc58ZXIjLFs_FgoVrd4Os8nJJkuSSWcSaf-9EzctG-mF5GLCmee8L-fMG0UvgSyBJfBhbwfXmnrZ2RaXBBRQJh5Fp5AyupCUsMdH_yfRM-_3hAimpHwanVCVCEIkO41WVyXGztYY2yLuhyaIxn7oOofeWxd_O1-f87hq4y32Js6wruMcTV-OpfK2szeVeR49KUzt8cV0nkU_P3-6Wn9dXFx-2axXF4tMprRfyALQcAaqKDBJYYtSpFJJkIIlGQjMcyOAUKU4QI6CYSoNiG1GDJdCJZKdRa8Pul1tvZ6m95oSSARNKYhAbA5Ebs1ed65qjLvV1lT6b8G6nTaur7IaNc2BcmpocGec00wpplSRES6MBIM8aH2c3IZtg3mGbe9MPROd37RVqXf2txaCAWdJEHg3CTh7PaDvdVP5cYGmRTt4DSnlknBIRq83_6APTzdROxMGqNrCBt9sFNUrnqajmFSBWj5AhS_HpspCVIoq1GcN72cNgenxpt-ZwXu9-fH9_9nLX3P27RFboqn70tt66Cvb-jnID2DmrPcOi_slA9Fj0u-2ocek6ynpoe3V8QPdN91Fm_0BNIj00g</recordid><startdate>20170727</startdate><enddate>20170727</enddate><creator>Kumar, Sandeep</creator><creator>Marriott, Claire E</creator><creator>Alhasawi, Nouf F</creator><creator>Bone, Adrian J</creator><creator>Macfarlane, Wendy M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7482-8906</orcidid></search><sort><creationdate>20170727</creationdate><title>The role of tumour suppressor PDCD4 in beta cell death in hypoxia</title><author>Kumar, Sandeep ; Marriott, Claire E ; Alhasawi, Nouf F ; Bone, Adrian J ; Macfarlane, Wendy M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6f1ea4318ffe791be65968616537c15edda510288411de53e96a15bc0a4658763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anoxia</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Sandeep</au><au>Marriott, Claire E</au><au>Alhasawi, Nouf F</au><au>Bone, Adrian J</au><au>Macfarlane, Wendy M</au><au>Palle, Komaraiah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of tumour suppressor PDCD4 in beta cell death in hypoxia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-07-27</date><risdate>2017</risdate><volume>12</volume><issue>7</issue><spage>e0181235</spage><epage>e0181235</epage><pages>e0181235-e0181235</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O2 (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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28750063</pmid><doi>10.1371/journal.pone.0181235</doi><tpages>e0181235</tpages><orcidid>https://orcid.org/0000-0002-7482-8906</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anoxia Apoptosis Apoptosis Regulatory Proteins - metabolism Beta cells Biology and Life Sciences Cell Death Cell Hypoxia Cell Line, Tumor Cell Proliferation Cell Survival Complications and side effects Cytology Cytoplasm Electron microscopy Exposure Gene expression Genetic aspects Hypoxia Immunocytochemistry Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Kinases Laboratories Medicine and Health Sciences Mice Mortality Pancreas Pancreatic beta cells Physical Sciences Physiological aspects Rats Research and Analysis Methods RNA-Binding Proteins - metabolism Rodents Scanning electron microscopy Staining Subcellular Fractions - metabolism Tumors Western blotting |
| title | The role of tumour suppressor PDCD4 in beta cell death in hypoxia |
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