title: Activation of p38 and changes in mitochondria accompany autophagy to premature senescence-like phenotype switch upon chronic exposure to selenite in colon fibroblasts.
abstract: Effects of chronic exposure to supranutritional sodium selenite (Se) were investigated in colonic fibroblasts. Initially, Se did not produce any gross changes in exposed cells; however, basal levels of autophagy were transiently increased and p38 activity was stimulated. From the 3rd week onwards, Se decreased cell proliferation, with corrensponding changes in cell cycle distribution. Also, in exposed cells oxidative stress and DNA damage slowly but gradually increased along with decreasing mitochondrial function and upon continued elevated activity of p38 kinase. Towards the end of the experiment, premature senescence features became more prominent in treated cells. Pharmacological inhibition as well as gene knockdown of these processes confirmed the involvement of p38 in balancing autophagy and premature senescence in cells exposed to Se and suggests that this element may in a given time frame compromise selected cell populations in digestive system.
authors.affiliation: Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 38 Hradec Králové, Czech Republic. Electronic address: rudolf@lfhk.cuni.cz.
authors.forename: Emil
authors.initials: E
authors.lastname: Rudolf
authors.affiliation: Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 38 Hradec Králové, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Rezáčová
authors.affiliation: Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 38 Hradec Králové, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Cervinka
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D018038:Sodium Selenite / Q000633:toxicity*; D013997:Time Factors; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases; D018038:Sodium Selenite
keywords: Autophagy; Colonic fibroblasts; Mitochondria; Premature senescence; Sodium selenite; p38