3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats

Latini, Alexandra; Rodríguez, María Cecilia; Rosa, Ricardo Abreu da; Scussiato, Karina; Leipnitz, Guilhian; Assis, Dênis Reis de; Ferreira, Gustavo da Costa; Funchal, Cláudia; Jacques-Silva, M. Caroline; Buzin, Luciane; Giugliani, Roberto; Cassina, Adriana; Radí, Rafael; Wajner, Moaçir

doi:10.1016/j.neuroscience.2005.05.013

Cited by 54 publications

(45 citation statements)

References 53 publications

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“…Ullrich and colleagues (1999) demonstrated that incubation of cortical slice cultures from rat with 4 mmol/L 3-OH-GA reduces complexes II and V activity. However, another study in cortical tissue homogenates from rats revealed only an inhibition of complex II by 3-OH-GA and no effect was found in homogenates from striata or in purified cortical mitochondria (Latini et al 2005).…”

Section: Bioenergetics: Secondary Excitotoxicity?mentioning

confidence: 90%

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Sauer

2007

J of Inher Metab Disea

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Glutaryl-CoA dehydrogenase (GCDH) is a central enzyme in the catabolic pathway of L-tryptophan, L-lysine, and L-hydroxylysine which catalyses the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO2. Glutaryl-CoA dehydrogenase deficiency (GDD) is an autosomal recessive disease characterized by the accumulation of glutaric and 3-hydroxyglutaric acids in tissues and body fluids. Untreated patients commonly present with severe striatal degeneration during encephalopathic crises. Previous studies have highlighted primary excitotoxicity as a trigger of striatal degeneration. The aim of this PhD study was to investigate in detail tissue-specific bioenergetic and biochemical parameters of GDD in vitro, post mortem, and in Gcdh-/- mice. The major bioenergetic finding was uncompetitive inhibition of alpha-ketoglutarate dehydrogenase complex by glutaryl-CoA. It is suggested that a synergism of primary and secondary excitotoxic effects in concert with age-related physiological changes in the developing brain underlie acute and chronic neurodegenerative changes in GDD patients. The major biochemical findings were highly elevated cerebral concentrations of glutaric and 3-hydroxyglutaric acid despite low permeability of the blood-brain barrier for these dicarboxylic acids. It can be postulated that glutaric and 3-hydroxyglutaric acids are synthesized de novo and subsequently trapped in the brain. In this light, neurological disease in GDD is not 'transported' to the brain in analogy with phenylketonuria or hepatic encephalopathy as suggested previously but is more likely to be induced by the intrinsic biochemical properties of the cerebral tissue and the blood-brain barrier.

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Section: Bioenergetics: Secondary Excitotoxicity?mentioning

confidence: 90%

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Sauer

2007

J of Inher Metab Disea

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“…The homogenates were centrifuged (1000 × g, 10 min, 4°C) and supernatant was centrifuged at 15000 × g in order to concentrate mitochondria in the pellet, which was dissolved in the same phosphate buffer (Latini et al, 2005). We then measured CS and complex I in mitochondria-enriched fractions (2 ml/mg protein) (Lowry et al, 1951).…”

Section: Biochemistrymentioning

confidence: 99%

Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice

et al. 2013

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Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice, Neuroscience (2013), doi: http://dx.doi.org/10.1016/j.neuroscience. 2013.03.039 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…The method described to determine this activity was slightly modified, as detailed in a previous report by Latini et al [35]. Enzyme activity was calculated as nmol/minute/mg protein.…”

Section: Determination Of Nadh Dehydrogenase Activitymentioning

confidence: 99%

Effects of Cadmium on Growth, Photosynthetic Pigments, Photosynthetic Performance, Biochemical Parameters and Structure of Chloroplasts in the Agarophyte <i>Gracilaria domingensis</i> (Rhodophyta, Gracilariales)

dos¹,

C.²,

P.³

et al. 2012

AJPS

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This paper aimed to evaluate the effects of different concentrations of cadmium on growth rates, photosynthetic pigments, photosynthetic performance, biochemical parameters and structure of chloroplasts in G. domingensis. To accomplish this, apical segments of G. domingensis were cultivated with different concentrations of cadmium, ranging from 100 to 300 μM, over a period of 16 days, and were processed for transmission electron microscopy analysis. The plants exposed to cadmium showed chloroplast alteration, especially degeneration of thylakoids and a decrease in the concentration of photosynthetic pigments, such as chlorophyll a and phycobiliproteins. However, the volume of plastoglobuli increased. As a defense mechanism, the plants treated with cadmium showed an increase in glutathione reductase activity. These results agree with the decreased photosynthetic performance and relative electron transport rate observed after exposure of algae to cadmium. Taken together, these findings strongly indicate that cadmium negatively affects the ultrastructure and metabolism of the agarophyte G. domingensis, thus posing a threat to the economic vitality of this red macroalga.

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3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats

Cited by 54 publications

References 53 publications

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice

Effects of Cadmium on Growth, Photosynthetic Pigments, Photosynthetic Performance, Biochemical Parameters and Structure of Chloroplasts in the Agarophyte <i>Gracilaria domingensis</i> (Rhodophyta, Gracilariales)

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3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats

Cited by 54 publications

References 53 publications

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Biochemistry and bioenergetics of glutaryl‐CoA dehydrogenase deficiency

Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice

Effects of Cadmium on Growth, Photosynthetic Pigments, Photosynthetic Performance, Biochemical Parameters and Structure of Chloroplasts in the Agarophyte &lt;i&gt;Gracilaria domingensis&lt;/i&gt; (Rhodophyta, Gracilariales)

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Effects of Cadmium on Growth, Photosynthetic Pigments, Photosynthetic Performance, Biochemical Parameters and Structure of Chloroplasts in the Agarophyte <i>Gracilaria domingensis</i> (Rhodophyta, Gracilariales)