Lead-Calcium Interactions and Lead Toxicity

Simons, T. J. B.

doi:10.1007/978-3-642-71806-9_24

Cited by 79 publications

(97 citation statements)

References 53 publications

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“…In this regard, it is of interest that a blockade of ␣1-ARs can help to reduce symptoms of PTSD (63), although it is not known if this helps rescue prefrontal cortical gray matter. Finally, an environmental toxin-lead-can mimic Ca 2ϩ , resulting in elevated PKC activity (64)(65)(66). The current results suggest that an increase in PKC signaling may contribute to a loss of prefrontal cortical gray matter in subjects with lead poisoning.…”

Section: Discussionmentioning

confidence: 71%

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Hains

Maciejewski

et al. 2009

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

202

186

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The prefrontal cortex r regulates behavior, cognition, and emotion by using working memory. Prefrontal functions are impaired by stress exposure. Acute, stress-induced deficits arise from excessive protein kinase C (PKC) signaling, which diminishes prefrontal neuronal firing. Chronic stress additionally produces architectural changes, reducing dendritic complexity and spine density of cortico-cortical pyramidal neurons, thereby disrupting excitatory working memory networks. In vitro studies have found that sustained PKC activity leads to spine loss from hippocampalcultured neurons, suggesting that PKC may contribute to spine loss during chronic stress exposure. The present study tested whether inhibition of PKC with chelerythrine before daily stress would protect prefrontal spines and working memory. We found that inhibition of PKC rescued working memory impairments and reversed distal apical dendritic spine loss in layer II/III pyramidal neurons of rat prelimbic cortex. Greater spine density predicted better cognitive performance, the first direct correlation between pyramidal cell structure and working memory abilities. These findings suggest that PKC inhibitors may be neuroprotective in disorders with dysregulated PKC signaling such as bipolar disorder, schizophrenia, post-traumatic stress disorder, and lead poisoning-conditions characterized by impoverished prefrontal structural and functional integrity. bipolar disorder ͉ post-traumatic stress disorder ͉ working memory ͉ chelerythrine ͉ lead poisoning

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Section: Discussionmentioning

confidence: 71%

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Hains

Maciejewski

et al. 2009

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

202

186

View full text Add to dashboard Cite

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“…Increased intracellular Ca 2+ , as the result of Ca 2+ influx or release from its internal storage, is the key step toward the promotion of the interactions between Ca 2+ -PKC and membrane phosphatidylserine (Huang and Huang, 1993). Pb 2+ is known to disturb intracellular Ca 2+ homeostasis (Pounds, 1984;Simons, 1993). The rise in total intracellular Ca 2+ by Pb treatment is thought to be due to Pb stimulation of Ca 2+ entry or inhibition of Ca 2+ exit/storage (Goldstein, 1977;Long and Rosen, 1992;Pounds et al, 1982;Rosen and Pounds, 1989;Schanne et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Zhao

Slavkovich

Zheng

1998

Toxicology and Applied Pharmacology

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Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood-brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood-CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 μM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1-10 μM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 μg Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood-CSF barrier in vitro, but not in vivo.The mammalian blood-cerebrospinal fluid (CSF) barrier resides primarily in the choroid plexus and plays a pivotal role in regulating the chemical stability of the central nervous system (Johanson, 1995;Davson and Segal, 1996). Toxic metals, especially lead (Pb), have been known to accumulate in the choroid plexus (Friedheim et al., 1983;Manton et al., 1984;O'Tuama et al., 1976;Zheng et al., 1991;Zheng, 1996). Our recent work revealed that accumulation of Pb in the choroid plexus is associated with a significant reduction in CSF concentrations of transthyretin (TTR), a major thyroxine-carrying protein in brain (Zheng et al., 1996). We postulated that Pb accumulation in the choroid plexus might also alter key enzymes that are apparently targeted by cellular Pb toxicity, such as the protein kinase C (PKC).

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“…Lead is multifactorial and directly interrupts enzyme activation, competitively inhibits trace mineral absorption, binds to sulfhydryl proteins (interrupting structural protein synthesis), alters calcium homeostasis, and lowers the level of available sulfhydryl antioxidant reserves in the body [25]. Moreover, lead disturbs intracellular Ca 2+ homeostasis and damages the endoplasmic reticulum, which in turn results in reduction of protein synthesis [26]. The inhibitory role of lead in protein synthesis may be due to its damaging effect on DNA and RNA [27].…”

Section: Resultsmentioning

confidence: 99%

Lead acetate induced oxidative stress and its possible reversal by Tribulus terrestris root extract in testes of Swiss albino mice

Khairwal¹

2013

IOSR-JESTFT

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Lead-Calcium Interactions and Lead Toxicity

Cited by 79 publications

References 53 publications

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Lead acetate induced oxidative stress and its possible reversal by Tribulus terrestris root extract in testes of Swiss albino mice

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