title: Oxysterols in adipose tissue-derived mesenchymal stem cell proliferation and death.
abstract: Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Potent effects in cell death processes, including cytoxicity and apoptosis induction, were described in several cell lines. Very little is known about the effects of oxysterols in MSCs. 7-ketocholesterol (7-KC), one of the most important oxysterols, was shown to be cytotoxic to human adipose tissue-derived MSCs. Here, we describe the short-term (24h) cytotoxic effects of cholestan-3α-5β-6α-triol, 3,5 cholestan-7-one, (3α-5β-6α)- cholestane-3,6-diol, 7-oxocholest-5-en-3β-yl acetate, and 5β-6β epoxy-cholesterol, on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from three young, healthy women. Oxysterols, with the exception of 3,5 cholestan-7-one and 7-oxocholest-5-en-3β-yl acetate, led to a complex mode of cell death that include apoptosis, necrosis and autophagy, depending on the type of oxysterol and concentration, being cholestan-3α-5β-6α-triol the most effective. Inhibition of proliferation was also promoted by these oxysterols, but no changes in cell cycle were observed.
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, room 43, 05403-000, São Paulo/SP, Brazil.
authors.forename: Suelen Feitoza
authors.initials: SF
authors.lastname: Silva
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, room 43, 05403-000, São Paulo/SP, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Levy
authors.affiliation: Federal University of Latin American Integration-UNILA, Life and Nature Science Institute, Av. Tarquinio Joslin dos Santos, 1000, Sala 105, CEP: 85870-901, Foz do Iguacu, Parana/PR, Brazil.
authors.forename: Jorge Luis Maria
authors.initials: JLM
authors.lastname: Ruiz
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, room 43, 05403-000, São Paulo/SP, Brazil.
authors.forename: Thatiana Correa
authors.initials: TC
authors.lastname: de Melo
authors.affiliation: Cell Culture and Wound Healing Research Laboratory, Division of Plastic Surgery, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Arnaldo, 455, 1st floor, 05403-000, São Paulo/SP, Brazil.
authors.forename: Cesar
authors.initials: C
authors.lastname: Isaac
authors.affiliation: Department of Earth and Exact Sciences, Federal University of São Paulo, São Paulo/SP, Brazil.
authors.forename: Maíra Luísa
authors.initials: ML
authors.lastname: Fidelis
authors.affiliation: Department of Earth and Exact Sciences, Federal University of São Paulo, São Paulo/SP, Brazil.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, room 43, 05403-000, São Paulo/SP, Brazil. Electronic address: spbydlow@usp.br.
authors.forename: Sérgio Paulo
authors.initials: SP
authors.lastname: Bydlowski
mesh_terms: D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D017209:Apoptosis; D001343:Autophagy; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival; D002776:Cholestanes / Q000494:pharmacology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007653:Ketocholesterols / Q000494:pharmacology; D008564:Membrane Potentials; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D010084:Oxidation-Reduction; D000072376:Oxysterols / Q000494:pharmacology*
chemical_list: D000199:Actins; D002776:Cholestanes; D007653:Ketocholesterols; D000072376:Oxysterols; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; C003001:7-ketocholesterol
keywords: Adipose tissue; Apoptosis; Cell death; Mesenchymal stem cell; Mitochondrial hyperpolarization; Oxysterol