| Age-dependent reduction of the PI3K regulatory subunit p85α suppresses pancreatic acinar cell proliferation. | |
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MedLine Citation:
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PMID: 22212451 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is important for tissue proliferation. Previously, we found that tissue regeneration after partial pancreatic resection was markedly attenuated in aged mice as compared to young mice and that this attenuation was because of an age-dependent reduction of PI3K/Akt signaling in the pancreatic acini; however, the mechanisms for the age-associated decline of pancreatic PI3K/Akt signaling remained unknown. To better delineate the mechanisms for the decreased PI3K/Akt activation with aging, age-associated changes in cell proliferation and PI3K/Akt signaling were investigated in the present study using in vitro primary pancreatic acinar cell cultures derived from young and aged mice. In response to treatment with insulin-like growth factor 1 (IGF-1), acinar cells from young but not aged mice showed increased activation of PI3K/Akt signaling and cell proliferation, indicating that intrinsic cellular mechanisms cause the age-associated changes in pancreatic acinar cells. We also found that the expression of PI3K p85α subunit, but not IGF-1 receptor or other PI3K subunits, was significantly reduced in pancreatic acinar cells from aged mice; this age-associated reduction of p85α was confirmed in both mouse and human pancreatic tissues. Finally, small interfering RNA (siRNA)-mediated knockdown of p85α expression in acinar cells from young mice resulted in markedly attenuated activation of PI3K/Akt downstream signaling in response to IGF-1. From these results, we conclude that exocrine pancreatic expression of PI3K p85α subunit is attenuated by aging, which is likely responsible for the age-associated decrease in activation of pancreatic PI3K signaling and acinar cell proliferation in response to growth-promoting stimuli. |
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Authors:
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Hitoshi Takahashi; Daiki Okamura; Marlene E Starr; Hiroshi Saito; B Mark Evers |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-02-01 |
Journal Detail:
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Title: Aging cell Volume: 11 ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-16 Completed Date: 2012-06-08 Revised Date: 2013-04-03 |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
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Languages: eng Pagination: 305-14 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
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Department of Surgery, University of Kentucky, Lexington, KY 40536, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acinar Cells
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cytology,
enzymology* Aging* Animals Cell Proliferation* Class Ia Phosphatidylinositol 3-Kinase / metabolism* Humans Insulin-Like Growth Factor I / metabolism Male Mice Mice, Inbred C57BL Pancreas / cytology, enzymology* Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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P01 DK035608/DK/NIDDK NIH HHS; R01 AG025273/AG/NIA NIH HHS; R01 AG025273/AG/NIA NIH HHS; R01 AG025908/AG/NIA NIH HHS; R01 AG025908/AG/NIA NIH HHS; R01 AG039732/AG/NIA NIH HHS; R01 AG039732/AG/NIA NIH HHS; R01 DK048498/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.137/Class Ia Phosphatidylinositol 3-Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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