Ascorbic acid (AA) is recognized as a free radical scavenger that protects cells from oxidative stress-induced damage. However, no studies have investigated the role of AA in acute alcoholic liver disease using senesc...Ascorbic acid (AA) is recognized as a free radical scavenger that protects cells from oxidative stress-induced damage. However, no studies have investigated the role of AA in acute alcoholic liver disease using senescence marker protein-30 (SMP30) knockout (KO) mice. SMP30 is a novel 34-kDa protein involved in AA biosynthesis. The present study aimed to elucidate the physiological functions of AA in acute ethanol-induced liver injury using SMP30 KO mice, which cannot synthesize AA in vivo. After a 4-week experimental period, mice were divided into six groups. The following three groups comprised the ethanol treatment groups: WT-E group (wild-type), KV-E group (AA-supplemented), and KT-E group (AA-deficient). Mice were exposed to an acute dose of ethanol (6 g ethanol/kg) administered by gavage once a day for three days. The other three control groups, namely, WT-C, KV-C, and KT-C control groups, received an equal volume of water via oral administration. Analysis of changes in body weight showed that mice in the KT-E group had significant loss of body weight compared to the control, KV-E, and WT-E groups. Behavioral analysis revealed that alcohol exposure significantly increased alcohol sensitivity in the KT-E group, whereas the WT-E, KV-E, and control groups developed ethanol tolerance. Aspartate transaminase (AST) levels in the KT-E group were significantly higher than those in the control, KV-E, and WT-E groups. The number of large and binucleated hepatocytes was significantly higher in the KT-E group than in the KV-E and WT-E groups. In addition, cytochrome P450 2E1 (CYP2E1) was over expressed in the central vein in the KT-E group when compared to the KV-E and WT-E groups. Our current findings indicate that AA supplementation in SMP30 KO mice can alleviate alcohol-induced liver damage by down regulating CYP2E1 expression. These results suggest that reduced CYP2E1 expression is a novel mechanism responsible for AA-induced reduction of ethanol-mediated oxidative stress.展开更多
糖代谢是癌症的一个典型特征,研究显示SMP30(senescence marker protein 30)是一种肝癌相关抗原,与脂代谢关系密切,为了探讨SMP30与糖代谢的变化是否相关,我们构建了稳定转染SMP30的人SK-HEP1肝癌细胞株。通过迁移实验、侵袭实验和CCK8...糖代谢是癌症的一个典型特征,研究显示SMP30(senescence marker protein 30)是一种肝癌相关抗原,与脂代谢关系密切,为了探讨SMP30与糖代谢的变化是否相关,我们构建了稳定转染SMP30的人SK-HEP1肝癌细胞株。通过迁移实验、侵袭实验和CCK8实验对比检测了过表达SMP30组与对照组肝癌细胞的迁移、侵袭、增殖的情况;同时还检测了细胞的葡萄糖吸收、乳酸排出的情况。结果显示,与对照组相比,SMP30对SK-HEP1肝癌细胞株的迁移、侵袭有明显的抑制作用(p<0.01);对细胞的增殖作用不明显(p>0.05)。过表达SMP30对肝癌细胞的葡萄糖吸收和乳酸排出作用不显著(p>0.05)。SMP30对肝癌细胞SK-HEP1的迁移、侵袭有一定的抑制作用,但这种作用与糖代谢关系不明显。展开更多
文摘Ascorbic acid (AA) is recognized as a free radical scavenger that protects cells from oxidative stress-induced damage. However, no studies have investigated the role of AA in acute alcoholic liver disease using senescence marker protein-30 (SMP30) knockout (KO) mice. SMP30 is a novel 34-kDa protein involved in AA biosynthesis. The present study aimed to elucidate the physiological functions of AA in acute ethanol-induced liver injury using SMP30 KO mice, which cannot synthesize AA in vivo. After a 4-week experimental period, mice were divided into six groups. The following three groups comprised the ethanol treatment groups: WT-E group (wild-type), KV-E group (AA-supplemented), and KT-E group (AA-deficient). Mice were exposed to an acute dose of ethanol (6 g ethanol/kg) administered by gavage once a day for three days. The other three control groups, namely, WT-C, KV-C, and KT-C control groups, received an equal volume of water via oral administration. Analysis of changes in body weight showed that mice in the KT-E group had significant loss of body weight compared to the control, KV-E, and WT-E groups. Behavioral analysis revealed that alcohol exposure significantly increased alcohol sensitivity in the KT-E group, whereas the WT-E, KV-E, and control groups developed ethanol tolerance. Aspartate transaminase (AST) levels in the KT-E group were significantly higher than those in the control, KV-E, and WT-E groups. The number of large and binucleated hepatocytes was significantly higher in the KT-E group than in the KV-E and WT-E groups. In addition, cytochrome P450 2E1 (CYP2E1) was over expressed in the central vein in the KT-E group when compared to the KV-E and WT-E groups. Our current findings indicate that AA supplementation in SMP30 KO mice can alleviate alcohol-induced liver damage by down regulating CYP2E1 expression. These results suggest that reduced CYP2E1 expression is a novel mechanism responsible for AA-induced reduction of ethanol-mediated oxidative stress.
文摘糖代谢是癌症的一个典型特征,研究显示SMP30(senescence marker protein 30)是一种肝癌相关抗原,与脂代谢关系密切,为了探讨SMP30与糖代谢的变化是否相关,我们构建了稳定转染SMP30的人SK-HEP1肝癌细胞株。通过迁移实验、侵袭实验和CCK8实验对比检测了过表达SMP30组与对照组肝癌细胞的迁移、侵袭、增殖的情况;同时还检测了细胞的葡萄糖吸收、乳酸排出的情况。结果显示,与对照组相比,SMP30对SK-HEP1肝癌细胞株的迁移、侵袭有明显的抑制作用(p<0.01);对细胞的增殖作用不明显(p>0.05)。过表达SMP30对肝癌细胞的葡萄糖吸收和乳酸排出作用不显著(p>0.05)。SMP30对肝癌细胞SK-HEP1的迁移、侵袭有一定的抑制作用,但这种作用与糖代谢关系不明显。
