Lead Enters Bovine Adrenal Medullary Cells Through Calcium Channels

Simons, T. J. B.; Pocock, G.

doi:10.1111/j.1471-4159.1987.tb04105.x

Cited by 146 publications

(70 citation statements)

References 26 publications

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“…These channels are involved in the uptake of calcium by neurons and across the blood-brain barrier. These channels are also permeable to lead, and thus lead may stimulate its own uptake, into the brain and into neurons, by activating PKC (47). Subjects with high PKC activity in the presence of lead may have higher brain lead levels for a given blood lead level.…”

Section: Discussionmentioning

confidence: 99%

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Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

Hwang

Lee

Bressler

et al. 2002

Environ Health Perspect

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At picomolar concentrations, lead activates protein kinase C (PKC). This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9), using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5, 2, and 5 of 14 interaction terms, respectively, had associated p-values less than 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead.

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Section: Discussionmentioning

confidence: 99%

“…Finally, PKC activity could be a surrogate measure for brain lead levels. Ion channels and transporters that participate in cellular homeostasis, including voltage-dependent calcium channels, are regulated, in part, by PKC (47)(48)(49). These channels are involved in the uptake of calcium by neurons and across the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

Hwang

Lee

Bressler

et al. 2002

Environ Health Perspect

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“…Indeed, it has been shown that Pb 2+ can be carried into cells via Ca 2+ channels Hinkle, 1997a, 1997b;Reuter, 1983;Simons, 1993;Simons and Pocock, 1987). Simons and Pocock (1987) used cells isolated from bovine adrenal medulla to demonstrate that Ca 2+ channels can mediate the uptake of Pb 2+ .…”

Section: Leadmentioning

confidence: 99%

“…Simons and Pocock (1987) used cells isolated from bovine adrenal medulla to demonstrate that Ca 2+ channels can mediate the uptake of Pb 2+ . Their data show that compounds, which depolarize the cell and subsequently open Ca 2+ channels, promote the uptake of Pb 2+ .…”

Section: Leadmentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

667

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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“…Studies conducted in preparations of mammalian small intestine support the existence of saturable and nonsaturable pathways of lead transfer and suggest that lead can interact with transport mechanisms for calcium and iron (see Section 3.4.2, Absorption). Lead can enter cells through voltagegated L-type Ca 2+ channels in bovine adrenal medullary cells (Legare et al 1998;Simons and Pocock 1987;Tomsig and Suszkiw 1991) and through store-operated Ca 2+ channels in pituitary GH3, glial C3, human embyronic kidney, and bovine brain capillary endothelial cells (Kerper andHinkle 1997a, 1997b).…”

Section: Soft Tissuesmentioning

confidence: 99%