کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278476 | 1295819 | 2007 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genome dynamics and transcriptional deregulation in aging
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کلمات کلیدی
MEFACTC1b2mLPLGAPDβ-2 microglobulin - β-2 میکروگلوبولینβ-actin - β-اکتینHydrogen peroxide - آب اکسیژنهGenome instability - بی ثباتی ژنومGene regulation - تنظیم ژنCell-to-cell variation - تنوع سلولی به سلولSomatic mutations - جهش های اجتماعیSingle cell - سلول تکActb - عملLipoprotein lipase - لیپو پروتئین لیپازmouse embryonic fibroblast - موش فیبروبلاست جنینیultraviolet light - نور ماوراءبنفش یا نور فرابنفشH2O2 - هیدروژن پراکسیدglyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Genome instability has been implicated as a major cause of both cancer and aging. Using a lacZ-plasmid transgenic mouse model we have shown that mutations accumulate with age in a tissue-specific manner. Genome rearrangements, including translocations and large deletions, are a major component of the mutation spectrum in some tissues at old age such as heart. Such large mutations were also induced by hydrogen peroxide (H2O2) in lacZ-plasmid mouse embryonic fibroblasts (MEFs) and demonstrated to be replication-independent. This was in contrast to ultraviolet light-induced point mutations, which were much more abundant in proliferating than in quiescent MEFs. To test if large rearrangements could adversely affect patterns of gene expression we PCR-amplified global mRNA content of single MEFs treated with H2O2. Such treatment resulted in a significant increase in cell-to-cell variation in gene expression, which was found to parallel the induction and persistence of genome rearrangement mutations at the lacZ reporter locus. Increased transcriptional noise was also found among single cardiomyocytes from old mice as compared with similar cells from young mice. While these results do not directly indicate a cause and effect relationship between genome rearrangement mutations and transcriptional deregulation, they do underscore the stochastic nature of genotoxic effects on cells and tissues and could provide a mechanism for age-related cellular degeneration in postmitotic tissue, such as heart or brain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 145, Issue 4, 14 April 2007, Pages 1341-1347
Journal: Neuroscience - Volume 145, Issue 4, 14 April 2007, Pages 1341-1347
نویسندگان
R. Busuttil, R. Bahar, J. Vijg,