PMID- 14672282 OWN - NLM STAT- MEDLINE DCOM- 20040128 LR - 20190402 IS - 0304-4920 (Print) IS - 0304-4920 (Linking) VI - 46 IP - 3 DP - 2003 Sep 30 TI - Homocysteine altered ROS generation and NO accumulation in endothelial cells. PG - 129-36 AB - Mild hyperhomocysteinemia (HHcy) is a risk factor for vascular disease and is closely associated with endothelial dysfunction. Oxidative stress and decreased nitric oxide (NO) bioavailability were reported in HHcy-induced vascular injury; however, the exact relationship is not understood. We thus directly determine the production of reactive oxygen species (ROS) and NO in cultured endothelial cells (HUVECs) to demonstrate the correlated variation between ROS and NO induced by Hcy (homocysteine), Cys (cysteine), another thiol compound, and Met (methionine), precursor of HHcy in animal study. HUVECs were treated with Hcy, Cys, or Met for 0.5 or 22-24 h; ROS generation was detected by DCF fluorescence with flow cytometry and NO by chemiluminescence. In non-cytotoxic (<1.0 mM) concentration ranges, Met exerted no effects on either ROS production or NO concentration, Cys decreased ROS production and increased NO in both short-term (0.5 h) and long-term (22-24 h) treatments; Hcy, however, induced a biphasic effect on ROS production, i.e., inhibitory at 0.5 h but stimulatory at 24 h. The maximal stimulation by Hcy (0.25 mM) was significantly reduced by co-incubation (12 h) with estrogen (1 microM). Hcy caused an early (0.5 h) increase of medium NO which was absent in long-term Hcy treatment. The oxidative stress caused by long-term Hcy incubation could be ameliorated by estrogen, consistent with earlier in vivo observations that estrogen prevents HHcy-induced injury. FAU - Tsen, Chih-Mei AU - Tsen CM AD - Department of Physiology and Pharmacology, Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC. FAU - Hsieh, Chien-Cheng AU - Hsieh CC FAU - Yen, Chia-Hung AU - Yen CH FAU - Lau, Ying-Tung AU - Lau YT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - India TA - Chin J Physiol JT - The Chinese journal of physiology JID - 7804502 RN - 0 (Reactive Oxygen Species) RN - 0LVT1QZ0BA (Homocysteine) RN - 31C4KY9ESH (Nitric Oxide) RN - AE28F7PNPL (Methionine) RN - K848JZ4886 (Cysteine) SB - IM MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cysteine/pharmacology MH - Endothelium, Vascular/cytology/*drug effects/*metabolism MH - Homocysteine/*pharmacology MH - Humans MH - Methionine/pharmacology MH - Nitric Oxide/*metabolism MH - Reactive Oxygen Species/metabolism MH - Umbilical Veins/cytology EDAT- 2003/12/16 05:00 MHDA- 2004/01/30 05:00 CRDT- 2003/12/16 05:00 PHST- 2003/12/16 05:00 [pubmed] PHST- 2004/01/30 05:00 [medline] PHST- 2003/12/16 05:00 [entrez] PST - ppublish SO - Chin J Physiol. 2003 Sep 30;46(3):129-36.