Liu Chun-Lin, Hsia Te-Chun, Yin Mei-Chin
Department of Neurosurgery, China Medical University Hospital, Taichung City, Taiwan.
Food Funct. 2014 Jun;5(6):1125-33. doi: 10.1039/c3fo60689a. Epub 2014 Apr 8.
A nerve growth factor-differentiated PC12 cell line was used to investigate the protective effects of s-methyl cysteine (SMC) at 1, 2, 4, and 8 μM under oxygen-glucose deprivation (OGD) conditions. OGD decreased the cell viability. However, SMC pre-treatments at 2, 4 and 8 μM improved the cell viability, decreased cleaved caspase-3 and Bax expression, and reserved Bcl-2 expression. Furthermore, SMC maintained the mitochondrial membrane potential, lowered the intracellular Ca(2+) concentration and DNA fragmentation, and decreased the activity and expression of caspase-3 and caspase-8. OGD increased the reactive oxygen species (ROS) and 3-nitrotyrosine production, decreased glutathione peroxide (GPX) and glutathione reductase (GR) activities and the expression, enhanced nitric oxide synthase (NOS) activity and inducible NOS (iNOS) expression. SMC pre-treatments at 2, 4 and 8 μM lowered the ROS and 3-nitrotyrosine formation, maintained GPX and GR activities and expression, and decreased NOS activity and iNOS expression. OGD up-regulated hypoxia-inducible factor (HIF)-1α, nuclear transcription factor kappa (NF-κ) B p50, NF-κB p65 and p-p38 expression. SMC pre-treatments at 1-8 μM lowered HIF-1α expression and decreased p38 phosphorylation. SMC at 2, 4 and 8 μM suppressed the protein expression of NF-κB p50 and NF-κB p65. When YC-1 (HIF-1α inhibitor), pyrrolidine dithiocarbamate (NF-κB inhibitor) or SB203580 (p38MAPK inhibitor) were used to block the activation of HIF-1α, NF-κB and p38, SMC pre-treatments did not affect the protein expression of HIF-1α, NF-κB and p-p38. These results indicated that SMC was a potent neuro-protective agent.
使用神经生长因子分化的PC12细胞系，研究了1、2、4和8μM的S-甲基半胱氨酸（SMC）在氧糖剥夺（OGD）条件下的保护作用。OGD降低了细胞活力。然而，2、4和8μM的SMC预处理提高了细胞活力，降低了裂解的半胱天冬酶-3和Bax表达，并保留了Bcl-2表达。此外，SMC维持了线粒体膜电位，降低了细胞内Ca(2+)浓度和DNA片段化，并降低了半胱天冬酶-3和半胱天冬酶-8的活性和表达。OGD增加了活性氧（ROS）和3-硝基酪氨酸的产生，降低了谷胱甘肽过氧化物酶（GPX）和谷胱甘肽还原酶（GR）的活性及表达，增强了一氧化氮合酶（NOS）活性和诱导型NOS（iNOS）表达。2、4和8μM的SMC预处理降低了ROS和3-硝基酪氨酸的形成，维持了GPX和GR的活性及表达，并降低了NOS活性和iNOS表达。OGD上调了缺氧诱导因子（HIF）-1α、核转录因子κB p50、NF-κB p65和p-p38表达。1-8μM的SMC预处理降低了HIF-1α表达并减少了p38磷酸化。2、4和8μM的SMC抑制了NF-κB p50和NF-κB p65的蛋白表达。当使用YC-1（HIF-1α抑制剂）、吡咯烷二硫代氨基甲酸盐（NF-κB抑制剂）或SB203580（p38丝裂原活化蛋白激酶抑制剂）阻断HIF-1α、NF-κB和p38的激活时，SMC预处理不影响HIF-1α、NF-κB和p-p38的蛋白表达。这些结果表明，SMC是一种有效的神经保护剂。
