Glucose-6-phosphate dehydrogenase and glutathione reductase support antioxidant enzymes in nerves and muscles of rats during nerve regeneration

Ninfali, Paolino; Cuppini, C; Marinoni, Silvia

doi:10.3233/rnn-1996-10202

Cited by 10 publications

(6 citation statements)

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“…Hereditary G6PD deficiencies, which are the most common human enzymopathies, may accordingly constitute an important risk factor for some neurodegenerative diseases. In addition to the neuroprotective relevance of G6PD itself in the adult brain, the expression of G6PD has been shown to be coordinately modulated with that of other antioxidative enzymes, including glutathione peroxidase and glutathione reductase, in the developing and adult rat brain. , The mechanism for this coordinated expression is unknown; however, it is thought that nerve growth factor (NGF) and insulin-like growth factor (IGF), which respond to changes in oxidant levels, may act as transcriptional regulators of these genes. , Hence, in addition to G6PD deficiencies, other antioxidative defense mechanisms may be compromised, which would increase susceptibility of the brain to ROS-mediated oxidative stress and subsequent neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

“…The levels of CuZnSOD mRNA and protein are particularly high in hippocampal pyramidal neurons and granular cells, which in the absence of adequate G6PD-mediated detoxification may result in H 2 O 2 overproduction and peroxidative damage within these cells. In addition to the cytoprotective role of G6PD against ROS-mediated oxidative damage, G6PD may be required for normal cell growth by providing NADPH for redox regulation. ,, …”

Section: Discussionmentioning

confidence: 99%

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Brain Glucose-6-phosphate Dehydrogenase Protects against Endogenous Oxidative DNA Damage and Neurodegeneration in Aged Mice

Jeng

Loniewska

Wells

2013

ACS Chem. Neurosci.

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Glucose-6-phosphate dehydrogenase (G6PD) protects the embryo from endogenous and xenobiotic-enhanced oxidative DNA damage and embryopathies. Here we show in aged mice that G6PD similarly protects against endogenous reactive oxygen species (ROS)-mediated neurodegeneration. In G6PD-normal (G6PD +/+ ) and heterozygous (G6PD +/def ) and homozygous (G6PD def/def ) G6PD-deficient male and female mice at about 2 years of age, oxidative DNA damage in various brain regions was assessed by 8-oxo-2′-deoxyguanosine formation using high-performance liquid chromatography and immunohistochemistry. Morphological changes in brain sections were assessed by H&E staining. DNA oxidation was increased in G6PD def/def mice in the cortex (p < 0.02), hippocampus (p < 0.01) and cerebellum (p < 0.006) compared to G6PD +/+ mice, and was localized to distinct cell types. Histologically, in G6PD +/def mice, enhanced regionally and cellularly specific neurodegenerative changes were observed in those brain regions exhibiting elevated DNA oxidation, with a 53% reduction in the Purkinje cell count. These results show G6PD is important in protecting against the neurodegenerative effects of endogenous ROS in aging, and suggest that common hereditary G6PD deficiencies may constitute a risk factor for some neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Brain Glucose-6-phosphate Dehydrogenase Protects against Endogenous Oxidative DNA Damage and Neurodegeneration in Aged Mice

Jeng

Loniewska

Wells

2013

ACS Chem. Neurosci.

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“…It is a substrate for NADPH oxidases in activated macrophages (Spolarics and Wu 1997) and polymorphonuclear leukocytes (Borregaard et al 1984) to produce oxygen radicals. It is necessary for reduction of oxidized glutathione by glutathione reductase (Romero et al 1991; Ninfali et al 1996). Finally, it is a substrate for biotransformation and detoxification enzymes (Winzer et al 2001).…”

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confidence: 99%

NADPH Production by the Pentose Phosphate Pathway in the Zona Fasciculata of Rat Adrenal Gland

Frederiks

Kümmerlin

Bosch

et al. 2007

J Histochem Cytochem.

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Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was approximately 60%, 15%, and 7% of G6PD activity, respectively. The K(m) value of G6PD for glucose-6-phosphate was two times higher than the K(m) value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.

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“…It is a substrate for NADPH oxidase in activated macrophages (Spolarics and Wu 1997) and polymorphonuclear leukocytes (Borregaard et al 1984) to produce oxygen radicals. It is necessary for reduction of oxidized glutathione by glutathione reductase (Romero et al 1991;Ninfali et al 1996) and is a substrate for phase I and II biotransformation and detoxification enzymes (Winzer et al 2001). G6PD is elevated in response to external stimuli (hormones, growth factors, nutrients, and toxic and oxidative stress; Swezey and Epel 1986;Stanton et al 1991;Kletzien et al 1994;Jonges et al 1995;Spolarics 1998;Amir-Ahmady and Salati 2001).…”

mentioning

confidence: 99%

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

Frederiks

Bosch

Jong

et al. 2003

J Histochem Cytochem.

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S U M M A R Y Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is the key regulatory enzyme of the pentose phosphate pathway and produces NADPH and riboses. In this study, the kinetic properties of G6PD activity were determined in situ in chemically induced hepatocellular carcinomas, and extralesional and control parenchyma in rat livers and were directly compared with those of the second NADPH-producing enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD). Distribution patterns of G6PD activity, protein, and mRNA levels were also compared to establish the regulation mechanisms of G6PD activity. In (pre)neoplastic lesions, the V max of G6PD was 150-fold higher and the K m for G6P was 10-fold higher than in control liver parenchyma, whereas in extralesional parenchyma, the V max was similar to that in normal parenchyma but the K m was fivefold lower. This means that virtual fluxes at physiological substrate concentrations are 20-fold higher in lesions and twofold higher in extralesional parenchyma than in normal parenchyma. The V max of PGD was fivefold higher in lesions than in normal and extralesional liver parenchyma, whereas the K m was not affected. Amounts of G6PD protein and mRNA were similar in lesions and in extralesional liver parenchyma. These results demonstrate that G6PD is strongly activated post-translationally in (pre)neoplastic lesions to produce NADPH.

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Glucose-6-phosphate dehydrogenase and glutathione reductase support antioxidant enzymes in nerves and muscles of rats during nerve regeneration

Cited by 10 publications

References 0 publications

Brain Glucose-6-phosphate Dehydrogenase Protects against Endogenous Oxidative DNA Damage and Neurodegeneration in Aged Mice

Brain Glucose-6-phosphate Dehydrogenase Protects against Endogenous Oxidative DNA Damage and Neurodegeneration in Aged Mice

NADPH Production by the Pentose Phosphate Pathway in the Zona Fasciculata of Rat Adrenal Gland

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

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