Learn More
The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain,(More)
The toxicity of L-3,4-dihydroxyphenylalanine (L-DOPA) was studied in neuronal cultures from rat mesencephalon. The survival and function of DA neurons were assessed by the number of tyrosine hydroxylase-positive (TH+) cells and 3H-DA uptake and those non-DA neurons by the exclusion of Trypan blue and the high-affinity 3H-GABA uptake. L-DOPA was toxic for(More)
Aralar, the neuronal Ca(2+)-binding mitochondrial aspartate-glutamate carrier, has Ca(2+) binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca(2+) with an S(0.5) of 324 nM. By employing primary neuronal(More)
PURPOSE Plitidepsin, given as a 1-hour weekly i.v. infusion for 3 consecutive weeks during a 4-week treatment cycle, was investigated in patients with solid tumors to determine the maximum tolerated dose and the recommended dose (RD) using this administration schedule. EXPERIMENTAL DESIGN Consecutive cohorts of patients with metastatic solid tumors or(More)
Aralar, the Ca(2+)-dependent mitochondrial aspartate-glutamate carrier expressed in brain and skeletal muscle, is a member of the malate-aspartate NADH shuttle. Disrupting the gene for aralar, SLC25a12, in mice has enabled the discovery of two new roles of this carrier. On the one hand, it is required for synthesis of brain aspartate and N-acetylaspartate,(More)
Levodopa, a dopamine (DA) precursor administered to patients with Parkinson's disease (PD), produces at 25-200 x 10(-6) M concentrations a dose-dependent reduction of 3H-DA uptake in foetal rat midbrain cultures. Also, a decrease in the number of viable cells and tyrosine hydroxylase (TH) positive neurones, plus disruption of the overall neuritic network(More)
Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport(More)
The aralar/AGC1 knockout (KO) mouse shows a drastic decrease in brain aspartate and N-acetylaspartate levels and global hypomyelination, which are attributed to the lack of neuron-produced NAA used by oligodendrocytes as precursor of myelin lipid synthesis. In addition, these mice have a gradual drop in brain glutamine synthesis. We show here that(More)
The method described herein provides a convenient and rapid procedure to obtain enriched neuronal cultures containing reproducible numbers of dopamine (DA) cells. These cultures allow experimental paradigms designed to study the effect of drugs on DA neurons without astroglial mediation. Neuronal-enriched cultures are prepared from the mesencephalon of rat(More)