Phospholipid Metabolism in Neural Microvascular Endothelial Cells after Exposure to Lead in Vitro

Bressler, Joseph; Forman, Sheila; Goldstein, Gary W.

doi:10.1006/taap.1994.1126

Cited by 19 publications

(7 citation statements)

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“…The presence of 0.02 or 0.2 mg% Pb 2+ did not significantly affect the accumulation of [ 3 H]-ArAc over 10 min exposure. These data are consistent with the requirement for a stimulant-dependent increase in intracellular Ca 2+ , since a Ca 2+ ionophore is needed to induce the Pb 2+ -dependent accumulation of ArAc in unstimulated cells [37]. However, 2.0 mg% Pb 2+ increased ArAc by more than twofold when compared to unstimulated controls, which indicates an acute toxic effect of this high dose.…”

Section: Discussionsupporting

confidence: 87%

“…This apparent reduction in plasma membrane integrity was consistent with the marked accumulation of ArAc ( Figure 6) and the known damaging effects of free fatty acids on membrane structures and functions. Ca 2+ -dependent tissue damage is known to involve the activation of lipases and the subsequent accumulation of unesterified fatty acids [37]. ArAc is always a major component of this fatty acid pool and it can be converted to a spectrum of eicosanoids, some of which add to the inflammatory response and ensuing damage.…”

Section: Discussionmentioning

confidence: 99%

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Lead‐dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscle

Dorman¹,

Freeman²

2002

J Biochem & Molecular Tox

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Lead (Pb(2+)) has been implicated in the development of hypertension and atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a central feature of both conditions and there is evidence that Pb(2+) potentiates serum-dependent cell growth. The aim of this work was to examine the role of phospholipase A(2) in mitogen-dependent VSMC proliferation and determine if Pb(2+) interacts with this system in order to potentiate mitotic events. It was observed that cell proliferation induced by angiotensin II, or fetal bovine serum, required the activation of a Ca(2+)-dependent cytosolic phospholipase A(2) and the subsequent release of unesterified arachidonic acid. This path was affected by Pb(2+) as the metal increased the amount of arachidonic acid accumulation induced by either mitogen. In addition, Pb(2+) potentiated mitogen-induced DNA synthesis when present at lower doses (0.02 or 0.2 mg%), but had no effect on DNA synthesis, or cell numbers, in unstimulated cells. However, a high dose (2 mg%) of Pb(2+) attenuated the DNA synthesis stimulated by angiotensin II, or serum, but induced the accumulation of unesterified arachidonic acid in unstimulated cells. A biphasic effect of Pb(2+) on cell numbers and viability was also observed as 0.02 or 0.2 mg% Pb(2+) did not affect cell numbers or trypan blue exclusion in unstimulated cells, while 2 mg% Pb(2+) reduced cell numbers and viability. It appeared, therefore, that the lower concentrations of Pb(2+) increased arachidonic acid release and DNA synthesis only in stimulated VSMC, perhaps due to further activation of a Ca(2+)-dependent processes. In contrast, the high dose of Pb(2+) reduced DNA synthesis in stimulated cells and reduced cell numbers and viability in unstimulated cells, which may relate to the noted increase in unesterified arachidonic acid.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Lead‐dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscle

Dorman¹,

Freeman²

2002

J Biochem & Molecular Tox

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“…Previous reports have shown that SK&F 96365 inhibited the Ca 2+ influx-dependent nitric oxide production in histamine-and thapsigargin-activated HUVECs [4,5]. It also inhibited PGI 2 formation in PAF-treated HUVECs [40] and reduced the stimulation of arachidonic acid release in bradykinin-stimulated renal cells [41] and in thapsigargintreated neural microvascular endothelial cells [42]. The current study demonstrates that, in the presence of transmembrane Ca 2+ gradient, SK&F 96365 inhibitory effects on histamine-or thapsigargin-elicited Ca 2+ rise are associated with a marked decrease in arachidonic acid release.…”

Section: Discussionmentioning

confidence: 96%

Regulation of Arachidonic Acid Release by Calcium Influx in Human Endothelial Cells

et al. 1999

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In response to stimuli, endothelial cells release arachidonic acid, a lipid precursor of various vasoactive substances. We have investigated the relationships between cytosolic Ca2+ movements and arachidonic acid release in human umbilical vein endothelial cells. Histamine, a receptor-dependent agonist, and thapsigargin, a specific inhibitor of sarco-/endoplasmic Ca2+ pumps, time- and dose-dependently increased the release of [1-14C]-arachidonic acid. This release was inhibited by AACOCF3, a selective inhibitor of cytosolic phospholipase A2 (PLA2). In the absence of Ca2+ influx, arachidonic acid release was suppressed in both histamine- and thapsigargin-stimulated cells, despite marked elevations of cytosolic Ca2+ concentration ([Ca2+]i). In the presence of Ca2+ influx, arachidonic acid release was reduced in cells treated with BAPTA, an intracellular Ca2+ buffer, or with SK&F 96365, a receptor-operated Ca2+ channel blocker. Arachidonic acid release was analyzed as a function of the two successive phases of Ca2+ response to stimulation: Ca2+ peak and plateau phase, reflecting Ca2+ mobilization from internal stores and Ca2+ influx, respectively. The amount of arachidonic acid released was directly related to [Ca2+]i values measured at the influx phase with a 80 nM [Ca2+]i threshold, similar to that reported for PLA2 translocation. This suggests that Ca2+ entry from the extracellular space is essential for activating cytosolic PLA2 in human endothelial cells.

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“…to PLA2 isoforms via their C2 domains. Previous studies have demonstrated either a direct activation of PLA2 by lead in vitro (Krug and Berndt, 1987;Krug et al, 1994) or a ionophoredependent activation of PLA2 by lead (Bressler et al, 1994) as measured by increases in free arachidonic acid. Recently, Osterode and Ulberth (2000) demonstrated increased concentrations of arachidonic acid in the red blood cells (RBC) of 12 lead-exposed adult men compared to 12 healthy, unexposed,…”

Section: Figmentioning

confidence: 99%

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

Bouton

Hossain

Frelin

et al. 2001

Toxicology and Applied Pharmacology

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Phospholipid Metabolism in Neural Microvascular Endothelial Cells after Exposure to Lead in Vitro

Cited by 19 publications

References 0 publications

Lead‐dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscle

Lead‐dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscle

Regulation of Arachidonic Acid Release by Calcium Influx in Human Endothelial Cells

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

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