title: Molecular mechanisms involved in the protective effect of selenocystine against methylmercury-induced cell death in human HepG2 cells.
abstract: Methylmercury (MeHg) has been recognized as a very toxic contaminant present in certain foodstuffs that adversely affects health and impairs the normal function of different organs. Experimental studies have shown that selenocompounds play an important role as cellular detoxificant and protective agents against the harmful effects of mercury. The present study examined the potential preventive activities of organic selenocompounds, focused on selenocystine (SeCys), against MeHg-induced toxicity in human HepG2 cells. Combined treatment of SeCys and MeHg protected HepG2 cells against MeHg-induced cell damage, showing this selenocompound a more relevant effect than those of selenium methylselenocysteine and selenium methionine. Co-treatment with SeCys exerted a protective effect against MeHg by restraining ROS generation and glutathione decrease, and through the modulation of antioxidant enzymes activities. In addition, SeCys delayed MeHg-induced apoptosis and prevented extracellular regulated kinases (ERKs) deactivation, as well as p38 and c-Jun N-terminal kinase (JNK) stimulations in comparison to MeHg-treated cells. ERK, JNK and p38 involvement on the protective effect of SeCys against MeHg-induced cell damage was confirmed by using selective inhibitors. All these results indicate that SeCys protects against MeHg-induced cell damage by modulating the redox status and key proteins related to cell stress and survival/proliferation pathways.
authors.affiliation: Departamento de Metabolismo y Nutrición, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cordero-Herrera
authors.forename: Susana
authors.initials: S
authors.lastname: Cuello
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Madrid
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Carmen
authors.initials: C
authors.lastname: Cámara
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016566:Organoselenium Compounds / Q000494:pharmacology*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017279:Selenocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D012645:Selenomethionine / Q000494:pharmacology
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; D020011:Protective Agents; D017382:Reactive Oxygen Species; D017279:Selenocysteine; C009226:selenocystine; D003553:Cystine; D012645:Selenomethionine; D010088:Oxidoreductases; D005978:Glutathione; C002979:selenomethylselenocysteine
keywords: 5-bromo-2′-deoxyuridine; Antioxidant and detoxificant defences; BrdU; CAT; Cell death; DTT; ERK; FBS; GPx; GR; GSH; HepG2 cells; JNK; LDH; MAPK; MeHg; Methylmercury; ROS; SeCys; SeMeSeCys; SeMet; Selenocystine; c-Jun N-terminal kinase; catalase; dithiotreitol; extracellular regulated kinase; fetal bovine serum; glutathione; glutathione peroxidase; glutathione reductase; lactate dehydrogenase; methylmercury; mitogen-activated protein kinases; reactive oxygen species; selenium methylselenocysteine; selenocystine; selenomethionine