title: Mechanism for the uncoupling of oxidative phosphorylation by juliprosopine on rat brain mitochondria.
abstract: Prosopis juliflora, popularly known as Algaroba, is a major problem because the lack of food during the driest times of the year and its high palatability and nutritional value make its fruits (pods) much appreciated by cattle, goats, sheep and other animals. However, the consumption of this plant for long periods can cause a disease called cara-torta (pie face), which is characterized by cranial nerve dysfunction, mainly due to the degeneration and disappearance of neurons in the trigeminal motor nucleus. Algaroba contains piperidine alkaloids that have been suggested as being responsible for its toxicity; one of these alkaloids is juliprosopine. This study was conducted to evaluate the mechanisms of action of juliprosopine in isolated rat brain mitochondria to evaluate the potential mechanisms that lead to neurotoxicity in animals intoxicated by algaroba. Juliprosopine stimulated state-4 respiration at concentrations of 10-25 μM, affected the membrane potential at all concentrations studied (5-25 μM) and affected ATP production only at higher concentrations (15 and 25 μM). Juliprosopine cannot be classified as a member of the protonophoric class of uncouplers, such as 2,4-dinitrophenol or CCCP (m-chlorophenylhydrazone), due to its inability to promote mitochondrial swelling in the hyposmotic medium of potassium acetate. In addition, carboxyatractyloside, Mg(2+), cyclosporine A and dithiothreitol did not protect the uncoupling induced by juliprosopine. Because juliprosopine increased the fluorescence responses of mitochondria labeled with 1-aniline-8-naphthalene sulfonate (ANS) and DPH (1,6-diphenyl-1,3,5-hexatriene), we suggested that its uncoupling action must be attributed to a modification of the arrangement of the inner mitochondrial membrane.
authors.affiliation: Laboratório de Bioquímica Metabólica e Toxicológica (LaBMeT), UNESP - Univ Estadual Paulista, Campus de Dracena, 17900-000 Dracena, SP, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Maioli
authors.forename: Danilo E C V
authors.initials: DE
authors.lastname: Lemos
authors.forename: Marieli
authors.initials: M
authors.lastname: Guelfi
authors.forename: Hyllana C D
authors.initials: HC
authors.lastname: Medeiros
authors.forename: Franklin
authors.initials: F
authors.lastname: Riet-Correa
authors.forename: Rosane M T
authors.initials: RM
authors.lastname: Medeiros
authors.forename: José M
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: Fábio E
authors.initials: FE
authors.lastname: Mingatto
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005453:Fluorescence; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000470:Alkaloids; C048175:juliflorine; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide