Lactate Up-Regulates the Expression of Lactate Oxidation Complex-Related Genes in Left Ventricular Cardiac Tissue of Rats

Autor(es)

Gabriel-Costa, Daniele ^[1] ; da Cunha, Telma Fatima ^[1] ; Grassmann Bechara, Luiz Roberto ^[1] ; Fortunato, Rodrigo Soares ^[2] ; Marchesi Bozi, Luiz Henrique ^[1] ; Coelho, Marcele de Almeida ^[1] ; Barreto-Chaves, Maria Luiza ^[3] ; Brum, Patricia Chakur ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[2] Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 5 MAY 21 2015.
• Citações Web of Science: 4

Resumo

Background Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex. Methods/Principal Findings Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM) added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O-2(center dot-)/H2O2) levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively) were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1 alpha and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O-2(center dot-)/H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1 alpha with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O-2(center dot-)/H2O2. Conclusions Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O-2(center dot-)/H2O2 driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in cardiac muscle. (AU)

• Processo FAPESP: 10/50048-1 - Bases celulares e funcionais do exercício físico na doença cardiovascular
• Beneficiário: Carlos Eduardo Negrão
• Modalidade de apoio: Auxílio à Pesquisa - Temático