Organic and inogranic lead inhibit neurite growth in vertebrate and invertebrate neurons in culture

Audesirk, Gerald; Shugarts, David; Nelson, Gina; Przekwas, Julie

doi:10.1007/bf02621263

Cited by 18 publications

(6 citation statements)

References 47 publications

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“…This total lead concentration is undoubtably much higher than the free lead concentration due to the chelating characteristics of cell culture medium. Measurements offree lead concentrations in cell culture medium with a lead-sensitive electrode by Audesirk et al (31) suggest that free lead levels in our experiments were in the nanomolar range. Thus, the current findings are consistent with our previous studies on leadinduced PKC translocation and enzyme activity in isolated 1 5 20 brain microvessels (11,12 also inhibited capillary-like tube formation (unpublished observation).…”

Section: Discussionsupporting

confidence: 46%

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Laterra¹,

Bressler²,

Indurti³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionsupporting

confidence: 46%

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Laterra¹,

Bressler²,

Indurti³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…If the only active forms of the metal are the free ionic Pb in culture and the plasma Pb in blood, then the Pb concentrations may be approximately equivalent. Otherwise, they may be over 100-fold different (Audesirk et al, 1989;Tiffany-Castiglioni, 1993;Lidsky and Schneider, 2003). Furthermore, the relatively high concentrations required to elicit trophic effects may reflect regional-specificity of Pb effects.…”

Section: Discussionmentioning

confidence: 96%

“…No direct correlation exists between the Pb concentration in neuronal culture and that found in the blood of symptomatic children. In culture models, some studies have found the free ionic Pb concentration to be 100-1,000-fold lower than the original concentration (Audesirk et al, 1989). In human samples, Pb concentration in plasma is over 100-fold lower (0.27-0.70%) than that of whole blood (Hernandez-Avila et al, 1998).…”

Section: Discussionmentioning

confidence: 98%

Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Davidovics¹,

DiCicco‐Bloom²

2005

J. Neurosci. Res.

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Lead (Pb) persists as an environmental toxicant despite aggressive environmental and occupational regulation. Neurotoxicological effects of acute Pb poisoning range from subtle cognitive deficits, to clumsiness and ataxia, to coma and seizures. In adult neurotoxicity, reductions of blood Pb levels are often associated with reversal of clinical signs. In children, however, the effects are more likely to endure, with even low levels of chronic Pb exposure correlating with decreasing IQ. These persistent effects likely result from neurodevelopmental insults, such as altered cell survival or maturation, although the mechanisms have not been fully defined. In the present study we define the effects of moderate-level Pb exposure on mammalian neurogenesis using a well-characterized cortical precursor model. Gestational day 14.5 rat cerebral cortical precursor cells were cultured in defined media and cell number, precursor proliferation, apoptosis, and neuritic process outgrowth were assessed following exposure to a range of Pb acetate concentrations. Surprisingly, whereas a concentration of 30 microg/ml Pb acetate was acutely toxic to neurons, concentrations between 1 and 10 microg/ml Pb acetate (approximately 3 microM and 30 microM Pb, respectively) increased cell number: 10 times as many cells exposed to 10 microg/ml Pb were present on day 4 as compared to control. The increase in cell number was not a result of increased proliferation, however, as DNA synthesis did not increase. Rather, Pb exposure maintained the survival of cortical precursors, as the progressive apoptosis occurring under control conditions was markedly reduced by the metal. Additionally, neuritic process initiation and outgrowth increased in a concentration-dependent manner, with processes four times as abundant on day 1 and twice as long on day 2. These results suggest that brief exposure to lead during neurogenesis directly affects cell survival and process development, potentially altering cortical arrangement. Consequently, alterations in neural circuitry may underlie some of the neurological effects of Pb exposure during brain development.

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“…One micromolar Pb is approximately 20 µg/dl, a blood lead level can be examined easily, and brain Pb levels are 1-3-times those of blood lead in rats (Bradbury and Deane 1993). In experiments, the concentration of free Pb 2+ is approximately 1/1000 of total Pb (Audesirk et al 1989). Cells were treated with 1.0 µM Pb acetate in FBS-containing medium for various times as described in the figure legends.…”

Section: Materials and Methods Cell Culture And Identificationmentioning

confidence: 99%

Lead-Induced Stress Response in Endoplasmic Reticulum of Astrocytes in CNS

Zhang

Sun

et al. 2008

Toxicology Mechanisms and Methods

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Lead is one of the most widespread toxicants in the environment, and its neurotoxicity contributes to a major medical issue. Numerous studies have shown that astrocytes are the main sites of Pb deposition in the central nervous system. A large amount of lead depositing in the astrocyte cells would result in the accumulation of unfolded protein in the endoplasmic reticulum (ER), which up-regulates the expression of molecular chaperones and meanwhile inhibits the cell-cycle progression and the transcription of certain proteins. The unfolded protein response (UPR) could down-regulate the expression of protein cyclinD1 and cause the stagnation of cell-cycle in primary-cultured astrocytes of rat. However, lead neither has obvious effects on the expression of C/EBP homologous protein (CHOP) nor achieves cell apoptosis in the progress of lead-induced UPR. When the stagnation of cell-cycle happens, glucose regulated protein of 78 kDa (GRP78) and other chaperones come to themselves to transport a body of unfolded-protein, consequently making cells survive.

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Organic and inogranic lead inhibit neurite growth in vertebrate and invertebrate neurons in culture

Cited by 18 publications

References 47 publications

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Lead-Induced Stress Response in Endoplasmic Reticulum of Astrocytes in CNS

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