| Increased ROS generation in subsets of OGG1 knockout fibroblast cells. | |
| | |
MedLine Citation:
|
PMID: 18006041 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oxoguanine DNA glycosylase (OGG1) is a major base excision repair protein responsible for excision of the mutagenic 8-oxoguanosine (8-oxoG) lesions from the genome. Despite OGG1's importance, the moderate phenotype of Ogg1-null (Ogg1(-/-)) mice is not well understood. This study addresses a mechanism by which Ogg1(-/-) cells limit accumulation of 8-oxoG in their genome. Our data reveal that a subset of Ogg1(-/-) cells shows higher ROS levels ((H)ROS cells), while approximately 85% of Ogg1(-/-) cells exhibit physiological levels of ROS ((L)ROS cells). Ogg1(-/-) cells were sorted based on their DCF fluorescence intensity to obtain (L)ROS and (H)ROS cell cultures. (L)ROS cultures proliferated at a rate comparable to Ogg1(+/+) and gradually accumulated cells exhibiting increased ROS and 8-oxoG levels. (L)ROS cells show a 2.8-fold increase in 8-oxoG level vs. (H)ROS cells (7-27-fold). Mitochondria of (H)ROS cells released more H(2)O(2) than (L)ROS and Ogg1(+/+) cells and were eliminated by apoptotic-like processes. These findings suggest that in the absence of OGG1, a surveillance system is activated that removes cells with extreme 8-oxoG levels from Ogg1(-/-) cultures. Whether similar mechanisms exists in tissues of Ogg1(-/-) mice is the focus of future investigations. |
| | |
Authors:
|
Attila Bacsi; Grzegorz Chodaczek; Tapas K Hazra; David Konkel; Istvan Boldogh |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-10-05 |
Journal Detail:
|
Title: Mechanisms of ageing and development Volume: 128 ISSN: 0047-6374 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2007 Nov-Dec |
Date Detail:
|
Created Date: 2007-12-31 Completed Date: 2008-03-06 Revised Date: 2011-01-12 |
Medline Journal Info:
|
Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
|
Languages: eng Pagination: 637-49 Citation Subset: IM |
Affiliation:
|
Department of Microbiology and Immunology, University of Texas Medical Branch ,Galveston, TX 77555, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis Cell Death Cell Proliferation Cells, Cultured DNA Glycosylases / deficiency, genetics, metabolism* Embryo, Mammalian Fibroblasts / metabolism*, pathology Genotype Guanosine / analogs & derivatives, metabolism Hydrogen Peroxide / metabolism Mice Mice, Inbred C57BL Mice, Knockout Mitochondria / metabolism Phenotype Reactive Oxygen Species / metabolism* Time Factors Transfection |
| Grant Support | |
ID/Acronym/Agency:
|
EOS 006677//PHS HHS; P01 AG021830/AG/NIA NIH HHS; P01 AG021830-020003/AG/NIA NIH HHS; P01 AI062885-01/AI/NIAID NIH HHS; P01 AI062885-020005/AI/NIAID NIH HHS; R01 CA102271-01A/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Reactive Oxygen Species; 118-00-3/Guanosine; 3868-31-3/8-hydroxyguanosine; 7722-84-1/Hydrogen Peroxide; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/Ogg1 protein, mouse |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Organochlorines and endometriosis: a mini-review.
Next Document: Priority pesticides and their degradation products in river sediments from Portugal.