Enzymatic Protection Against Peroxidative Damage in Isolated Brain Capillaries

Tayarani, Ivan; Chaudière, Jean; Lefauconnier, Jeanne-Marie; Bourre, Jean‐Marie

doi:10.1111/j.1471-4159.1987.tb05677.x

Cited by 79 publications

(38 citation statements)

References 28 publications

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“…4). Brain capillary endothelium contains a high level of antioxidants, such as superoxide dismutase, glutathione peroxidase, or catalase (Tayarani et al, 1987). The latter two may eliminate H 2 O 2 effectively at resting pH i in RBCE cells, but their activity could be diminished in pronounced intracellular acidosis, due to protonation at critical sites.…”

Section: Discussionmentioning

confidence: 99%

Impaired Regulation of pH Homeostasis by Oxidative Stress in Rat Brain Capillary Endothelial Cells

et al. 2005

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(1) Endothelial cells are permanently challenged by altering pH in the blood, and oxidative damage could also influence the intracellular pH (pH(i)) of the endothelium. Cerebral microvascular endothelial cells form the blood-brain barrier (BBB) and pH(i) regulation of brain capillary endothelial cells is important for the maintenance of BBB integrity. The aim of this study was to address the pH regulatory mechanisms and the effect of an acute exposure to hydrogen peroxide (H2O2) on the pH regulation in primary rat brain capillary endothelial (RBCE) cells The RBCE monolayers were loaded with the fluorescent pH indicator BCECF and pH(i) was monitored by detecting the fluorescent changes. (2) The steady-state pH(i) of RBCE cells in HEPES-buffer (6.83 +/- 0.1) did not differ significantly from that found in bicarbonate-buffered medium (6.90 +/- 0.08). Cells were exposed to NH4CI to induce intracellular acidification and then the recovery to resting pH was studied. Half-recovery time after NH4Cl prepulse-induced acid load was significantly less in the bicarbonate-buffered medium than in the HEPES-medium, suggesting that in addition to the Na+ / H+ exchanger, HCO3- / Cl- exchange mechanism is also involved in the restoration of pH(i) after an intracellular acid load in primary RBCE cells. We used RT-PCR-reactions to detect the isoforms of Na+ / H+ exchanger gene family (NHE). NHE-1 -2, -3 and -4 were equally present, and there was no significant difference in the relative abundance of the four transcripts in these cells. (3) No pH(i) recovery was detected when the washout after an intracellular acid load occurred in nominally Na+ -free HEPES-buffered medium or in the presence of 10 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a specific inhibitor of Na+ / H+ exchanger. The new steady-state pH(i) were 6.37 +/- 0.02 and 6.60 +/- 0.02, respectively. (4) No detectable change was observed in the steady-state pH(i) in the presence of 100 microM H2O2; however, recovery from NH4Cl prepulse-induced intracellular acid load was inhibited when H2O2 was present in 50 or 100 microM concentration in the HEPES-buffered medium during NH4Cl washout. These data suggest that H2O2 is without effect on the activity of Na+ / H+ exchanger at rest, but could inhibit the function of the exchanger after an intracellular acid load.

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Section: Discussionmentioning

confidence: 99%

Impaired Regulation of pH Homeostasis by Oxidative Stress in Rat Brain Capillary Endothelial Cells

et al. 2005

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“…They protect cells from peroxidative damage. On the other hand, the BBB cells are innately loaded with easily peroxidizable polyunsatured fatty acids; this makes the BBB more vulnerable to oxidative damage and to lipid peroxidation in particular [97].…”

Section: Viral Proteins and Oxidative Stress In Brain Endothelial Cellsmentioning

confidence: 99%

The Blood-Brain Barrier in NeuroAIDS

Banks

Erçal²,

Price³

2006

CHR

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Nearly every aspect of blood-brain barrier (BBB) function is involved in or affected by HIV-1. The disruption of the BBB tends to be minimal and is not likely the mechanism by which infected immune cells and virus enter the brain. Instead, immune cells, virus and viral proteins likely activate brain endothelial cells and enable their own passage across the BBB by way of highly regulated processes such as diapedesis and adsorptive endocytosis. Viral proteins and cytokines can enter the CNS from the blood and provide a mechanism by which HIV-1 can affect CNS function independent of viral transport. Brain endothelial cells can also secrete neuroimmunoactive substances when stimulated by HIV-1, gp120, and Tat. Efflux systems such as p-glycoprotein transport anti-virals in the brain-to-blood direction, thus hampering effective accumulation of drug by the CNS. Overall, the BBB plays a major role in establishing and maintaining virus within the CNS and neuroAIDS.

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“…This may be interpreted as indicating that generated hydroxyl radical cannot penetrate basal and cell membrane of intact microvessels. Alternatively, endothelial cells and pericytes possess enough antioxidants and scavenger enzymes [34] to oppose the mild, in progress oxidative stress induced by Fe 2+ ions.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine synthesis‐related enzyme activities of bovine brain microvessels exhibit susceptibility to peroxidation

et al. 1996

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In microvessels isolated from bovine brain, microsomal enzyme activities involved in phosphatidylcholine biosynthesis and degradation were determined. The microvessels possessed acyl-CoA:l-acyl-sn-glycero-3-phosphoeholine (AT) and glycerophosphocholine phosphodiesterase (GroPChoPDE) activity at a higher level compared with bovine and rat brain or rat liver microsomes whereas they expressed CTP:phosphocholine cytidylyltransferase (CT) and choline phosphotransferase (CPT) activity at a lower level. Each enzyme has been characterized in terms of response to inldbitors or activators revealing properties very similar to those in brain and liver microsomes. In the homogenate prepared from t-butylhydroperoxide-treated microvessels (10 min exposure to 10 ~ up to 1 mM concentrations), AT and CPT activities exhibited a significant dose-dependent inhibition. In contrast, GroPChoPDE activity was unaffected. CT was inhibited only at 1 mM concentration. Short treatment of microvessels with Fe 2÷ (20 ~Vl)-ascorbate (0.25 mM) or 100 ~VI linoleate hydroperoxide did not have any effect on the activity of the four enzymes. Strong inhibition of all enzymes was noted when the linoleate hydroperoxide system was fortified by Fe 2÷ ions (100 ttM). AT inactivation was also found when oxidized low density lipoprotein was preincubated with microvessels. On the other hand, oxidized LDL left unchanged CPT and GroPChoPDE activities whereas it promoted a slight stimulation of cytidylyltransferase activity. Overall, the results suggest a link between oxygen radical generation and the perturbation of the microvessel membrane structure in which the four enzymes are incorporated, coupled to a direct sulfhydryl protein modification.

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Enzymatic Protection Against Peroxidative Damage in Isolated Brain Capillaries

Cited by 79 publications

References 28 publications

Impaired Regulation of pH Homeostasis by Oxidative Stress in Rat Brain Capillary Endothelial Cells

Impaired Regulation of pH Homeostasis by Oxidative Stress in Rat Brain Capillary Endothelial Cells

The Blood-Brain Barrier in NeuroAIDS

Phosphatidylcholine synthesis‐related enzyme activities of bovine brain microvessels exhibit susceptibility to peroxidation

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