Synergistic effects of s-Adenosylhomocysteine and homocysteine on DNA Damage in a murine microglial cell line

doi:10.1016/j.cca.2007.01.007

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 保健營養系(所) > 期刊論文 > Item 310902800/22189

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標題:	Synergistic effects of s-Adenosylhomocysteine and homocysteine on DNA Damage in a murine microglial cell line
作者:	Pei-Ying Lin Tsai-Hsiu Yang Hung-Gi Lin Miao-Lin Hu
貢獻者:	保健營養系
關鍵字:	S-adenosylhomocysteine Homocysteine DNA damage DNA hypomethylation Reactive oxygen species Synergy
日期:	2007-04
上傳時間:	2010-01-11 14:08:14 (UTC+8)
摘要:	Background Homocysteine (Hcy) and S-adenosylhomocysteine (SAH) are 2 major metabolites of methionine. However, little is known about their interactions in human diseases. Methods We determined the interaction of Hcy with SAH on DNA damage (measured as comet formation) and DNA hypomethylation (assayed as 5-methyldeoxycytidine, 5-mdc) in BV-2 cells (immortalized murine microglia). Results Hcy at 100 μmol/l and SAH at 4 μmol/l alone caused little DNA strand breaks, whereas 100 μmol/l Hcy in combination with 0.5 to 4 μmol/l SAH led to marked DNA damage and uracil misincorporation. The combination of 100 μmol/l Hcy with 4 μmol/l SAH (SAH + Hcy) significantly increased intracellular H2O2, and the DNA damage induced by SAH + Hcy was strongly inhibited by addition of superoxide dismutase, catalase or desferrioxamine, suggesting the involvement of reactive oxygen species. DNA damage induced by SAH + Hcy may also involve DNA hypomethylation (i.e., decreased %5-mdc) because of the high correlation between them. The effects induced by SAH + Hcy were specific to SAH but not to Hcy because they were markedly decreased by replacing SAH with adenosine (4.0 μmol/l) but was not affected by replacing Hcy with cysteine (100 μmol/l). Conclusion SAH in combination with Hcy can cause synergistic DNA damage in BV-2 cells. It remains to be seen whether some of the Hcy-related diseases may be caused by a collaborative action of Hcy with SAH.
關聯:	Clinica chimica Acta 379(1-2)： p.139-144
显示于类别:	[保健營養系(所) ] 期刊論文

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