Decreased ras–mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients
dc.contributor.author | Deng, Chun | en_US |
dc.contributor.author | Kaplan, Mariana J. | en_US |
dc.contributor.author | Yang, Jun | en_US |
dc.contributor.author | Ray, Donna | en_US |
dc.contributor.author | Zhang, Zhiyong | en_US |
dc.contributor.author | McCune, William Joseph | en_US |
dc.contributor.author | Hanash, Samir M. | en_US |
dc.contributor.author | Richardson, Bruce C. | en_US |
dc.date.accessioned | 2006-04-19T13:27:14Z | |
dc.date.available | 2006-04-19T13:27:14Z | |
dc.date.issued | 2001-02 | en_US |
dc.identifier.citation | Deng, Chun; Kaplan, Mariana J.; Yang, Jun; Ray, Donna; Zhang, Zhiyong; McCune, W. Joseph; Hanash, Samir M.; Richardson, Bruce C. (2001)."Decreased ras–mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients." Arthritis & Rheumatism 44(2): 397-407. <http://hdl.handle.net/2027.42/34297> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34297 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11229472&dopt=citation | en_US |
dc.description.abstract | Objective Previous studies have shown that inhibiting T cell DNA methylation causes a lupus-like disease by modifying gene expression. T cells from patients with lupus exhibit diminished levels of DNA methyltransferase (MTase) enzyme activity, hypomethylated DNA, and changes in gene expression similar to those exhibited by T cells treated with methylation inhibitors, suggesting that DNA hypomethylation may contribute to human lupus. Since it is known that DNA MTase levels are regulated by the ras–mitogen-activated protein kinase (MAPK) pathway, this study sought to determine whether decreased ras-MAPK signaling could account for the DNA hypomethylation in lupus T cells. Methods DNA MTase messenger RNA (mRNA) from lupus patients and from healthy controls was quantitated by Northern analysis, and ras-MAPK signaling was determined by immunoblotting with antibodies to the activated forms of extracellular receptor–associated kinase (ERK). Results were compared with those in T cells in which ras-MAPK signaling was inhibited with a soluble inhibitor of MAPK ERK 1 (MEK1). Results T cells from patients with active lupus had diminished DNA MTase mRNA levels and decreased signaling through the ras-MAPK pathway. Inhibiting signaling through the ras-MAPK pathway with the MEK1 inhibitor decreased DNA MTase mRNA and enzyme activity to the levels seen in lupus T cells, and resulted in DNA hypomethylation resembling that seen in lupus T cells. Conclusion These results suggest that a decrease in signaling through the ras-MAPK pathway may be responsible for the decreased MTase activity and DNA hypomethylation in patients with lupus. | en_US |
dc.format.extent | 2962351 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Inc. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Decreased ras–mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, Michigan ; 5310 Cancer Center and Geriatrics Center Building, Ann Arbor, MI 48109-0940 | en_US |
dc.identifier.pmid | 11229472 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34297/1/59_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/1529-0131(200102)44:2<397::AID-ANR59>3.0.CO;2-N | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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