title: N-acetyl-serotonin protects HepG2 cells from oxidative stress injury induced by hydrogen peroxide.
abstract: Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2 produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Shuna
authors.initials: S
authors.lastname: Yu
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Zhengchen
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yu
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Du
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departments of Anatomy, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D012701:Serotonin; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D053148:Caspase 3; D053453:Caspase 9; C006389:N-acetylserotonin