Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system

Song, Jin H.; Shin, Seon H.; Ross, Gregory M.

doi:10.1016/s0006-8993(01)02029-7

Cited by 70 publications

(46 citation statements)

References 53 publications

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“…Lipid Peroxide Determination-The amount of lipid peroxides in membranes was quantified by the thiobarbituric acid-reactive substance assay (29). The samples were mixed with 1 ml of 0.67% thiobarbituric acid and 0.5 ml of 20% tricholoroacetic acid, and the mixtures were incubated in a boiling water bath for 20 min.…”

Section: Preparation Of Substrates For the Ipla 2 Assay-[mentioning

confidence: 99%

Involvement of Calcium-independent Phospholipase A2in Hydrogen Peroxide-induced Accumulation of Free Fatty Acids in Human U937 Cells

Balboa

Balsinde

2002

Journal of Biological Chemistry

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Previous studies have demonstrated that U937 cells are able to mobilize arachidonic acid (AA) and synthesize prostaglandins in response to receptor-directed and soluble stimuli by a mechanism that involves the activation of Group IV cytosolic phospholipase A 2 ␣. In this paper we show that these cells also mobilize AA in response to an oxidative stress induced by H 2 O 2 through a mechanism that appears not to be mediated by cytosolic phospholipase A 2 ␣ but by the calcium-independent Group VI phospholipase A 2 (iPLA 2 ). This is supported by the following lines of evidence: (i) the response is essentially calcium-independent, (ii) it is inhibited by bromoenol lactone, and (iii) it is inhibited by an iPLA 2 antisense oligonucleotide. Enzyme assays conducted under a variety of conditions reveal that the specific activity of the iPLA 2 does not change as a result of H 2 O 2 exposure, which argues against the activation of a specific signaling cascade ending in the iPLA 2 . Rather, the oxidant acts to perturb membrane homeostasis in a way that the enzyme susceptibility/accessibility to its substrate increases, and this results in altered fatty acid release. In support of this view, not only AA, but also other fatty acids, were found to be liberated in an iPLA 2 -dependent manner in the H 2 O 2 -treated cells. Collectively, these studies underscore the importance of the iPLA 2 in modulating homeostatic fatty acid deacylation reactions and document a potentially important route under pathophysiological conditions for increasing free fatty acid levels during oxidative stress.

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Section: Preparation Of Substrates For the Ipla 2 Assay-[mentioning

confidence: 99%

Involvement of Calcium-independent Phospholipase A2in Hydrogen Peroxide-induced Accumulation of Free Fatty Acids in Human U937 Cells

Balboa

Balsinde

2002

Journal of Biological Chemistry

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“…23) Furthermore, several studies in vitro have shown that AA also has pro-oxidant properties, and induces lipid peroxidation and apoptosis in neuronal cells. [24][25][26] Thus, it is unclear whether continuous oral administration of AA can protect against a transient cerebral ischemia in diabetic state.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Oral Administrated Ascorbic Acid against Oxidative Stress and Neuronal Damage after Cerebral Ischemia/Reperfusion in Diabetic Rats

Iwata

Okazaki

Kamiuchi

et al. 2010

JOURNAL OF HEALTH SCIENCE

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Diabetes enhances oxidative stress and exacerbates acute ischemic injury. Previous studies have demonstrated that infarct volumes were greater in diabetic animals caused by a transient cerebral ischemia as compared with nondiabetic animals. Ascorbic acid (AA) as a naturally occurring major antioxidant is reported to be low in diabetic tissues. Therefore, we examined the effects of daily supplementation of AA on lipid peroxidation and the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in streptozotocin (STZ)-induced diabetic rat brain. Additionally, we also investigated whether AA improves the exacerbation of neuronal damage induced by middle cerebral artery occlusion followed by reperfusion (MCAO/Re) in diabetic state. Type1-diabetes was induced in male Sprague Dawley rats by STZ (60 mg/kg of intraperitoneal injection). Five weeks after STZinjection, the diabetic rats showed enhanced lipid peroxidation and impaired activity of antioxidant enzymes in the brain. Furthermore, the gene expression of glucose transporter GLUT1, which locates in the endothelial cells of the blood-brain-barrier and transports oxidized AA as the main source of AA supply to the brain, was downregulated in the diabetic brain. AA-supplemented (100 mg/kg daily, 2 weeks) diabetic rats showed normal levels of all these parameters. A diabetic state markedly aggravated MCAO/Re-induced neurological deficits and cerebral injury assessed by infarction volume. Treatment of AA remarkably improved both parameters in the diabetic rats. These results suggest that daily intake of AA relieves the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to improvement of augmented oxidative stress.

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“…The effects triggered by the accumulation of DHA in neurons have begun to be elucidated recently. The first studies were focused in determining the effect of the extracellular oxidation of AA over the redox state of the neuron, showing that incubation of brain slices with exogenous AA produces an increase in thiobarbituric acid reactive substances (TBARS) [46][47][48], an indicator of oxidative damage. However, this effect was prevented by treatment with glutathione, indicating that AA oxidation might induce an increase in reactive oxygen species (ROS).…”

Section: Effects Of Dha In Neuronsmentioning

confidence: 99%

“…AA creates the conditions for the Fenton reaction to occur, so AA might induce an increase in ROS and trigger cell death due to extracellular accumulation of H 2 O 2 [49,50]. Nevertheless, no increase in TBARS occurs when DHA uptake is prevented by inhibition of GLUT1 in brain slices, indicating that the pro-oxidant effect requires DHA uptake by nervous cells and does not depend directly on AA oxidation and accumulation of H 2 O 2 [47]. Additionally, as previously described, the pro-oxidant effect Vitamin Cof AA disappears when it is co-incubated with glutathione, even when glutathione reduces DHA into AA [33].…”

Section: Effects Of Dha In Neuronsmentioning

confidence: 99%

Vitamin C Transporter (SVCT2) Distribution in Developing and Adult Brains

Ferrada¹,

Salazar²,

Santander³

2017

Vitamin C

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Vitamin C is the major antioxidant molecule in the central nervous system (CNS), reaching concentrations of 10 mM in neurons and 400 μM in the cerebrospinal fluid (CSF). Uptake of vitamin C by brain cells is performed through the co-transporter of ascorbic acid and sodium isoform 2, SVCT2, which is expressed in cells from the choroid plexus, neurons, oligodendrocytes, and ependymal cells. SVCT2 expression has also been described in cells at the neurogenic niche, specifically in proliferative type C cells. In this chapter, we will describe recently published studies of SVCT2 expression during brain development and define its polarization in cells from the radial glia (neuronal precursors within the CNS) and vitamin C-mediated effects in regulating genes associated with the maintenance of CNS stem cell pluripotency. We will discuss the differential biological effect that vitamin C generates in neurons versus astrocytes and how the oxidized form of vitamin C, dehydroascorbic acid (DHA), produced by neurons in conditions of oxidative stress must leave this cell to be incorporated by astrocytes. In this context, we will discuss recent literature, which shows that DHA regulates glycolytic metabolism in neurons. In parallel, we will analyze vitamin C recycling by astrocytes, which reduce DHA into ascorbic acid (AA), increasing the antioxidant potential of the brain. Data discussed in this chapter will provide an updated view of SVCT2 distribution in the brain and will also describe how vitamin C recycling participates in normal or pathological brain function.

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Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system

Cited by 70 publications

References 53 publications

Involvement of Calcium-independent Phospholipase A2in Hydrogen Peroxide-induced Accumulation of Free Fatty Acids in Human U937 Cells

Involvement of Calcium-independent Phospholipase A2in Hydrogen Peroxide-induced Accumulation of Free Fatty Acids in Human U937 Cells

Protective Effects of Oral Administrated Ascorbic Acid against Oxidative Stress and Neuronal Damage after Cerebral Ischemia/Reperfusion in Diabetic Rats

Vitamin C Transporter (SVCT2) Distribution in Developing and Adult Brains

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