| A positive role of phosphatidylinositol 3-kinase in aging phenotype expression in cultured human diploid fibroblasts. | |
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MedLine Citation:
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PMID: 12849077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In order to detect the role that phosphatidylinositol 3-kinase (PI3K) plays in the aging of human diploid fibroblasts, we analyzed cellular inositol phospholipids and expression of PI3Ks. In aged cells a decrease in phosphatidylinositol 3,4-bisphosphate (PI3,4P(2)) was notable, while phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 4,5-bisphosphate (PI4,5P(2)) decreased slightly. On the other hand, the messages of PI3K IIalpha, Vps34, and p110delta decreased and that of PI3K IIbeta increased during aging. These changes might relate to the aging phenomena, with the PI3K subspecies functioning differentially. Consistently, a PI3K inhibitor LY294002 greatly suppressed enlargement and flattening of cell body and nucleus as well as cell proliferation, both phenotypes being typical of aged cells. An oxidative stress, pulse exposure to hydrogen peroxide (H(2)O(2)), induced these senescent cell-like phenotypes, which LY294002 was also able to abolish. Upon examining three different cell systems (HL-60, N1E-115, and PC-12 cells) we found clear parallelism in a cellular event between the dependence on a PI3K activity and the sensitivity to H(2)O(2). On the analogy of these relationships, we could hypothesize that expression of an aging phenotype such as the morphogenesis is positively promoted by some PI3K subspecies, if such a phenotype as cell cycling is negatively affected by attenuation of another PI3K function in the course of cellular aging. |
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Authors:
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Koozi Matuoka; Kuang Yu Chen; Tadaomi Takenawa |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Archives of gerontology and geriatrics Volume: 36 ISSN: 0167-4943 ISO Abbreviation: Arch Gerontol Geriatr Publication Date: 2003 May-Jun |
Date Detail:
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Created Date: 2003-07-09 Completed Date: 2003-10-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8214379 Medline TA: Arch Gerontol Geriatr Country: Ireland |
Other Details:
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Languages: eng Pagination: 203-19 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan. kmatuoka@mailhost.net |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
genetics,
physiology* Age Factors Cell Aging* / drug effects, physiology Cell Cycle Cell Line Cells, Cultured Chromatography, Thin Layer Chromones / pharmacology Culture Media DNA Primers Densitometry Diploidy Fibroblasts / cytology Gene Expression Humans Hydrogen Peroxide / pharmacology Morpholines / pharmacology Nucleic Acid Amplification Techniques Oxidative Stress Phenotype Phosphatidylinositols / analysis RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Chromones; 0/Culture Media; 0/DNA Primers; 0/Morpholines; 0/Phosphatidylinositols; 0/RNA, Messenger; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 7722-84-1/Hydrogen Peroxide; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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