The highly efficient powerhouse in the Wistar audiogenic rat, an epileptic rat strain

Autor(es)

Porto Dechandt, Carlos Roberto ^[1] ; Vicentini, Tatiane M. ^[1] ; Lanfredi, Guilherme Pauperio ^[2] ; Silva-Jr, Rui M. P. ; Espreafico, Enilza Maria ^[3] ; Cortes de Oliveira, Jose A. ^[4] ; Faca, Vitor Marcel ^[2] ; Garcia-Cairasco, Norberto ^[4] ; Alberici, Luciane Carla ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto, SP - Brazil

^[3] Silva-Jr, Jr., Rui M. P., Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY; v. 316, n. 3, p. R243-R254, MAR 2019.
• Citações Web of Science: 1

Resumo

The Wistar audiogenic rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister x brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of oxidative phosphorylation, oxidative stress, biogenesis, and dynamics in liver, skeletal muscle, and heart of male WARs and correlating them with physiological aspects of body metabolism. The results showed higher mitochondrial content, respiration rates in phosphorylation and non-coupled states, and H2O2 production in WARs. Liver presented higher content of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1 alpha) and mammalian target of rapamycin, proteins related to mitochondrial biogenesis. In agreement, isolated liver mitochondria from WARs showed higher respiration rates in phosphorylation state and ADP-to-O ratio, as well as higher content of proteins related to electron transport chain ATP synthase, TCA cycle, and mitochondrial fusion and fission compared with their Wistar counterparts. Mitochondria with higher area and perimeter and more variable shapes were found in liver and soleus from WARs in addition to lower reduced-to-oxidized glutathione ratio. In vivo, WARs demonstrated lower body mass and energy expenditure but higher food and water intake and amino acid oxidation. When exposed to a running test, WARs reached higher speed and resisted for a longer time and distance than their Wistar controls. In conclusion, the WAR strain has mitochondrial changes in liver, skeletal muscle, and heart that improve its mitochondrial capacity of ATP production, making it an excellent rat model to study PGC1 alpha overexpression and mitochondrial function in different physiological conditions or facing pathological challenges. (AU)

• Processo FAPESP: 16/23509-4 - Identificação de miocinas neuroprotetoras liberadas pelo músculo esquelético humano em contração de baixa e alta intensidades: papel da bioenergética mitocondrial e do estresse oxidativo
• Beneficiário: Luciane Carla Alberici
• Modalidade de apoio: Auxílio à Pesquisa - Regular