Maralani M Naderi, Movahedian A, Javanmard Sh Haghjooy
Department of Clinical Biochemistry and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R.Iran .
Res Pharm Sci. 2012 Oct;7(4):209-15.
Oxidative stress has been implicated as a prominent determinant in the development of several diseases such as atherosclerosis. Anti atherosclerotic effects of L-serine have been shown previously but its responsible mechanisms remained unidentified. This study aimed to investigate the antioxidant and cytoprotecrtive effects of L-serine and its possible mechanisms. For this purpose, cell viability analysis and nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) activity, heme oxygenase-1 (HO-1) concentration, total Nitric Oxide (NOx) production were evaluated in oxidative stress-induced Human Umbilical Vein Endothelial Cells (HUVECs) pretreated by L-serine. Cytoprotective effects of L-serine was measured through 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Nrf2 activity and HO-1 concentration were determined in the cell lysate by commercial immunoassay methods. NOx was assayed in the supernatant of culture medium through colorimetric Griess method. Pretreatment with L-serine (0.1-3.2 mM) protected endothelial cells from hydrogen peroxide-mediated cell cytotoxicity (H(2)O(2), 0.5 mM) and lead to significant induction of Nrf2 activity, HO-1 expresssion and NOx production. These findings demonstrated that L-serine has antioxidant and cytoprotective effects through the elevation of some crucial antioxidant factors such as Nrf2, HO-1 and NO.
氧化应激被认为是动脉粥样硬化等多种疾病发展的一个重要决定因素。L-丝氨酸的抗动脉粥样硬化作用此前已有报道,但其作用机制尚不明确。本研究旨在探讨L-丝氨酸的抗氧化和细胞保护作用及其可能的机制。为此,在氧化应激诱导的人脐静脉内皮细胞(HUVECs)中,用L-丝氨酸预处理后,评估细胞活力分析、核因子红系2(NF-E2)相关因子2(Nrf2)活性、血红素加氧酶-1(HO-1)浓度、总一氧化氮(NOx)生成量。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定L-丝氨酸的细胞保护作用。通过商业免疫分析方法测定细胞裂解液中的Nrf2活性和HO-1浓度。通过比色法Griess法测定培养基上清液中的NOx。用L-丝氨酸(0.1-3.2 mM)预处理可保护内皮细胞免受过氧化氢介导的细胞毒性(H2O2,0.5 mM),并导致Nrf2活性、HO-1表达和NOx生成显著诱导。这些发现表明,L-丝氨酸通过提高一些关键的抗氧化因子如Nrf2、HO-1和NO发挥抗氧化和细胞保护作用。