title: 1,25-Dihydroxyvitamin D3prevents deleterious effects of homocysteine on mitochondrial function and redox status in heart slices.
abstract: Because homocysteine (Hcy) is a risk factor for cardiovascular disease, and vitamin D deficiency can contribute to cardiovascular pathologies. In the present study, we tested the hypothesis that Hcy could impair energy metabolism, mitochondrial function, and redox status in heart slices of Wistar rats and that 1,25-dihydroxivitamin D3(calcitriol) treatment could prevent such effects. Heart slices were first pretreated with 3 different concentrations of calcitriol (50, 100, and 250nmol/L) for 30minutes at 37°C, after which Hcy was added to promote deleterious effects on metabolism. After 1 hour of incubation, the samples were washed, homogenized, and stored at -80°C before analysis. The results showed that Hcy caused changes in energy metabolism (respiratory chain enzymes), mitochondrial function, and cell viability. Homocysteine also induced oxidative stress, increasing lipid peroxidation, reactive oxygen species generation, and protein damage. An imbalance in antioxidant enzymes was also observed. Calcitriol (50nmol/L) reverted the effect of Hcy on the parameters tested, except for the immunocontent of catalase. Both treatments (calcitriol and Hcy) did not alter the vitamin D receptor immunocontent, which combined with the fact that our ex vivo model is acute, suggesting that the beneficial effect of calcitriol occurs directly through antioxidative mechanisms and not via gene expression. In this study, we show that Hcy impairs mitochondrial function and induces changes in the redox status in heart slices, which were reverted by calcitriol. These findings suggest that calcitriol may be a preventive/therapeutic strategy for complications caused by Hcy.
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.; Laboratory of Neuroprotection and Neurometabolic Diseases, Department of Biochemistry, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Longoni
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.; Laboratory of Neuroprotection and Neurometabolic Diseases, Department of Biochemistry, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Janaina
authors.initials: J
authors.lastname: Kolling
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.; Laboratory of Neuroprotection and Neurometabolic Diseases, Department of Biochemistry, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Cassiana
authors.initials: C
authors.lastname: Siebert
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Dos Santos
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Jussemara Souza
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Letícia F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Leo Anderson
authors.initials: LA
authors.lastname: Meira-Martins
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: de Assis
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.; Laboratory of Neuroprotection and Neurometabolic Diseases, Department of Biochemistry, Universidade Federal of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil.. Electronic address: wyse@ufrgs.br.
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002470:Cell Survival; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D006710:Homocysteine; D014807:Vitamin D; D002117:Calcitriol
keywords: Calcitriol; Energy metabolism; Heart slices; Homocysteine; Mitochondria function; Redox status