Abamectin affects the bioenergetics of liver mitochondria: A potential mechanism of hepatotoxicity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da abamectina na bioenergética de mitocôndrias isoladas de fígado de rato: Juliana Carla Castanha Zanoli. -

Pós-graduação em Ciência Animal - FMVA

Mecanismos da infertilidade causada por Gossipol em ratos e efeito protetor da vitamina E

Pós-graduação em Ciência e Tecnologia Animal - FEIS

Expressão gênica de Xanthomonas citri subsp. citri colonizando laranja doce ‘pêra rio’ (Citrus sinensis (L.) Osbeck) e lima ácida ‘galego’ (Citrus aurantifolia Swingle)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Arabidopsis thaliana Uncoupling Proteins (AtUCPs): insights into gene expression during development and stress response and epigenetic regulation

Mitochondrial inner membrane uncoupling proteins (UCP) catalyze a proton conductance that dissipates the proton electrochemical gradient established by the respiratory chain, thus affecting the yield of ATP synthesis. UCPs are involved in mitochondrial energy flow regulation and have been implicated in oxidative stress tolerance. Based on the global gene expression profiling datasets available for Arabidopsis thaliana, in this review we discuss the regulation of UCP gene expression during development and in response to stress, and provide interesting insights on the possible existence of epigenetic regulation of UCP expression.

Dehydromonocrotaline inhibits mitochondrial complex 1. A potential mechanism accounting for hepatotoxicity of monocrotaline

Monocrotaline is a pyrrolizidine alkaloid present in plants of the Crotalaria species, which causes cytotoxicity and genotoxicity, including hepatotoxicity in animals and humans. It is metabolized by cytochrome P-450 in the liver to the alkylating agent dehydromonocrotaline. We evaluated the effects of monocrotaline and its metabolite on respiration, membrane potential and ATP levels in isolated rat liver mitochondria, and on respiratory chain complex I NADH oxidase activity in submitochondrial particles. Dehydromonocrotaline, but not the parent compound, showed a concentration-dependent inhibition of glutamate/malate-supported state 3 respiration (respiratory chain complex 1), but did not affect succinate-supported respiration (complex II). Only dehydromonocrotaline dissipated mitochondrial membrane potential, depleted ATP, and inhibited complex I NADH oxidase activity (IC50 = 62.06 mu M) through a non-competitive type of inhibition (K-I = 8.1 mu M). Therefore, dehydromonocrotaline is an inhibitor of the activity of respiratory chain complex I NADH oxidase, an action potentially accounting for the well-documented monocrotaline's hepatotoxicity to animals and humans. The mechanism probably involves change of the complex I conformation resulting from modification of cysteine thiol groups by the metabolite. (c) 2007 Elsevier Ltd. All rights reserved.

Cytotoxicity of monocrotaline in isolated rat hepatocytes: Effects of dithiothreitol and fructose

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aspectos toxicológicos do bissulfito e outros agentes tóxicos sobre a síntese de glicerol-3-fosfato desidrogenase citoplasmá tica de levedura de panificação

The synthesis of intracellular glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) in baker's yeast was investigated in submerged culture supplied with glucose or glycerol as sole carbon sources. Inhibitors of the glycolytic pathway, Krebs cycle and respiratory chain did not stimulate glycerol-3-phosphate dehydrogenase synthesis when added in low concentrations in up 7.5 × 10 -5 mol/L. The repression exercised by glucose on the synthesis of glycerol-3-phosphate dehydrogenase in YP-glucose medium was reduced by the addition of fermentation products and of sodium bisulfite. Synthesis of the enzyme was raised 22-110%. However, in YP-glycerol medium, the addition of 0.06% (w/v) sodium bisulfite reduced (29%) the synthesis of the enzyme, while 0.012% (v/v) acetaldehyde stimulated the synthesis of glycerol-3-phosphate dehydrogenase by 12%.

Energy Metabolism in Cardiac Remodeling and Heart Failure

Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. © 2013 by Lippincott Williams & Wilkins.

Análise funcional das proteínas desacopladas mitocondriais de plantas utilizando RNA-seq e mutantes de inserção

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fipronil na bioenergética de mitocôndrias isoladas de figado de rato

Pós-graduação em Ciência Animal - FMVA

Transcriptome response signatures associated with the overexpression of a mitochondrial uncoupling protein (AtUCP1) in tobacco

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of fipronil on energy metabolism in the perfused rat liver

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative effects of fipronil and its metabolites sulfone and desulfinyl on the isolated rat liver mitochondria

Fipronil is an insecticide extensively used to control pests in crops and animals. There are relates of poisoning due to exposure of fipronil in mammals and the liver has been suggested as potential target. In this study, we evaluated the effects of fipronil and its metabolites sulfone and desulfinyl on the bioenergetics, reactive oxygen species (ROS) production and calcium efflux from mitochondria isolated from rat liver. Fipronil (5-25 μM) inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. Fipronil also caused uncoupling in succinate-energized mitochondria and calcium efflux. The metabolites sulfone and desulfinyl also acted as mitochondrial inhibitors and uncouplers and caused calcium efflux, but with different potencies, being the sulfone the more potent one. These effects of fipronil and its metabolites on mitochondrial bioenergetics and calcium homeostasis may be related to toxic effects of the insecticide in the liver.

Mecanismos de toxicidade dos metabólitos do fipronil, dessulfinil e sulfona, em mitocôndrias isoladas de fígado de rato

Pós-graduação em Ciência e Tecnologia Animal - FEIS