RESUMO
Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to accumulated evidence that hypometabolism, manifested in humans as reduced brain glucose consumption, is a principal factor in acquired epilepsy. Therefore, targeting deficient energy metabolism may be an effective approach for treating epilepsy. To confront this pathology we utilized pyruvate, which besides being an anaplerotic mitochondrial fuel possesses a unique set of neuroprotective properties as it: (i) is a potent reactive oxygen species scavenger; (ii) abates overactivation of Poly [ADP-ribose] polymerase 1 (PARP-1); (iii) facilitates glutamate efflux from the brain; (iv) augments brain glycogen stores; (v) is anti-inflammatory; (vi) prevents neuronal hyperexcitability; and (vii) normalizes the cytosolic redox state. In vivo, chronic oral pyruvate administration completely abolished established epileptic phenotypes in three accepted and fundamentally different rodent acquired epilepsy models. Our study reports metabolic correction by pyruvate as a potentially highly effective treatment of acquired epilepsies.
Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Ácido Pirúvico/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ondas Encefálicas/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Excitação Neurológica , Masculino , Camundongos Transgênicos , Pentilenotetrazol , Ratos Sprague-Dawley , Toxina TetânicaRESUMO
The role of 14C-aminoacyl-tRNAs in the formation of aminoacyl phosphatidyl glycerols in isolated chloroplasts of haricot bean leaves was studied. The formation of 14C-aminoacyl-tRNAs was more intensive in the case when 14C-aminoacyl phosphatidyl glycerols were the source of amino acids. On incubation of lamellae with 14C-aminoacyl phosphatidyl glycerols, 14C-amino acids proved to be incorporated intensively in protein of the lamellae. Membrane-bound chloroplast ribosome-like particles were observed on the outermost thylakoid membranes of the grana stacks as well as on the stroma thylakoids. It is concluded that aminoacyl phosphatidyl glycerols play an important role in lateral transport of amino acids within the chloroplasts lamellar system.
Assuntos
Cloroplastos/metabolismo , Fosfatidilgliceróis/fisiologia , Aminoacil-RNA de Transferência/metabolismo , Aminoácidos/metabolismo , Transporte Biológico , Fabaceae/citologia , Fabaceae/metabolismo , Membranas/metabolismo , Fosfatidilgliceróis/biossíntese , Plantas MedicinaisRESUMO
The composition of membrane phospholipids during chloroplast biogenesis was studied. The maximal level of phosphatidic acid was observed in the membrane fraction of proplastids. Phosphatidylglycerol was found to be the most abundant phospholipid component of grana thylakoids. The evidence from the in vivo experiments indicates that phosphatidic acid and phosphatidylglycerol incorporate the 32P label at a high rate at all stages of the chloroplast biogenesis. It is concluded that plastids are the site of the phosphatidylglycerol biosynthesis in the plant cell.