Transport of Toxic Heavy Metals Across Cell Membranes

Abstract

Abstract. Membrane transport of nonessential toxic heavy metals (type D heavy metals) not only controls their access to intracellular target sites but also helps determine their uptake, distribution, and excretion from the body. The critical role of membranes in the toxicology of class D metals has attracted the attention of many investigators, and extensive information has been collected on the mechanism(s) of metal transfer across membranes. Characteristics of metal transport in different cells, or even on opposite sides of the same cell, or under different physiological conditions, are not identical, and no unitary hypothesis has been formulated to explain this process in all cells. However, it seems possible that the mechanisms proposed for different cells represent variations on a few common themes.

Atomic force microscopy investigation of morphological changes in living keratinocytes treated with HgCl2 at not cytotoxic doses

“…These clots (see arrows in Fig. 6b), having lateral size of few microns and height less than 1 μm (see height profile of line 2 of Figs 6a in Fig 6c), could be cellular material binding the mercury ions (through sulphydril groups) which is ejected from the cell (Foulkes, 2000).…”

Atomic force microscopy investigation of morphological changes in living keratinocytes treated with HgCl2 at not cytotoxic doses

“…These clots (see arrows in Fig. 6b), having lateral size of few microns and height less than 1 μm (see height profile of line 2 of Figs 6a in Fig 6c), could be cellular material binding the mercury ions (through sulphydril groups) which is ejected from the cell (Foulkes, 2000).…”

Heme-Regulated eIF2α Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress

“…It is well documented that lead can cause adverse health effects, including neurotoxicity, nephrotoxicity, and hematological disorders and cardiovascular malfunctions . Lead in blood is able to induce oxidative damage in circulating blood cells and cause erythrocyte destruction through the formation of lipid peroxides in the cell membrane. , For acute lead toxicity, anemia is primarily due to hemolysis. , However, under chronic lead poisoning, anemia is caused by multiple factors, including insufficient erythrocyte production and hemolysis. ,, Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions . Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far.…”

“…27,52,53 Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions. 54 Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far. For example, the binding of Pb 2+ to protein sulfydryl groups would result in inhibition of ALA-D activity, leading to heme deficiency, and reduction of heme supply is a known reason for lead-related pathology.…”

Heavy Metals Affect Nematocysts Discharge Response and Biological Activity of Crude Venom in the JellyfishPelagia noctiluca(Cnidaria, Scyphozoa)

“…On a cellular level, the interaction of heavy metals with cell membrane transport mechanisms is the basis for their effect on biological systems. Examples of this interaction are given by Foulkes [50], describing the internalization of metals inside the cell, and Yu et al [51], describing an alteration of the activity of epithelial sodium channels (ENaC) following divalent heavy metals exposure.…”

“…In this regard, the latter authors reported that the mechanism of toxin action mainly depends on pore-forming into the membrane of cell target rather than oxidative damage, since GSH, cysteine and ascorbic acid did not impair the hemolytic power. Based on these observations, an intriguing hypothesis is that the interaction of metals with cell membrane [50] or crude venom components may reduce the hemolytic activity of venom by impairing the binding and insertion of pore-forming toxins in the membrane of target cells. Accordingly, Miyake et al [62] explained the inhibitory effect of divalent cations upon Vibrio metschnikovii cytolysin by changes in the erythrocytes membrane fluidity, so that pore formation due to the toxin was impaired, while, on the other hand, Iwase et al [63] suggested that extracellular Ca 2+ may accelerate the rate of removal of the toxin by endocytosis.…”

Atomic force microscopy investigation of morphological changes in living keratinocytes treated with HgCl2 at not cytotoxic doses

“…These clots (see arrows in Fig. 6b), having lateral size of few microns and height less than 1 μm (see height profile of line 2 of Figs 6a in Fig 6c), could be cellular material binding the mercury ions (through sulphydril groups) which is ejected from the cell (Foulkes, 2000).…”

Heme-Regulated eIF2α Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress

“…It is well documented that lead can cause adverse health effects, including neurotoxicity, nephrotoxicity, and hematological disorders and cardiovascular malfunctions . Lead in blood is able to induce oxidative damage in circulating blood cells and cause erythrocyte destruction through the formation of lipid peroxides in the cell membrane. , For acute lead toxicity, anemia is primarily due to hemolysis. , However, under chronic lead poisoning, anemia is caused by multiple factors, including insufficient erythrocyte production and hemolysis. ,, Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions . Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far.…”

“…27,52,53 Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions. 54 Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far. For example, the binding of Pb 2+ to protein sulfydryl groups would result in inhibition of ALA-D activity, leading to heme deficiency, and reduction of heme supply is a known reason for lead-related pathology.…”

Heavy Metals Affect Nematocysts Discharge Response and Biological Activity of Crude Venom in the JellyfishPelagia noctiluca(Cnidaria, Scyphozoa)

“…On a cellular level, the interaction of heavy metals with cell membrane transport mechanisms is the basis for their effect on biological systems. Examples of this interaction are given by Foulkes [50], describing the internalization of metals inside the cell, and Yu et al [51], describing an alteration of the activity of epithelial sodium channels (ENaC) following divalent heavy metals exposure.…”

“…In this regard, the latter authors reported that the mechanism of toxin action mainly depends on pore-forming into the membrane of cell target rather than oxidative damage, since GSH, cysteine and ascorbic acid did not impair the hemolytic power. Based on these observations, an intriguing hypothesis is that the interaction of metals with cell membrane [50] or crude venom components may reduce the hemolytic activity of venom by impairing the binding and insertion of pore-forming toxins in the membrane of target cells. Accordingly, Miyake et al [62] explained the inhibitory effect of divalent cations upon Vibrio metschnikovii cytolysin by changes in the erythrocytes membrane fluidity, so that pore formation due to the toxin was impaired, while, on the other hand, Iwase et al [63] suggested that extracellular Ca 2+ may accelerate the rate of removal of the toxin by endocytosis.…”

Atomic force microscopy investigation of morphological changes in living keratinocytes treated with HgCl2 at not cytotoxic doses

“…These clots (see arrows in Fig. 6b), having lateral size of few microns and height less than 1 μm (see height profile of line 2 of Figs 6a in Fig 6c), could be cellular material binding the mercury ions (through sulphydril groups) which is ejected from the cell (Foulkes, 2000).…”

Heme-Regulated eIF2α Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress

“…It is well documented that lead can cause adverse health effects, including neurotoxicity, nephrotoxicity, and hematological disorders and cardiovascular malfunctions . Lead in blood is able to induce oxidative damage in circulating blood cells and cause erythrocyte destruction through the formation of lipid peroxides in the cell membrane. , For acute lead toxicity, anemia is primarily due to hemolysis. , However, under chronic lead poisoning, anemia is caused by multiple factors, including insufficient erythrocyte production and hemolysis. ,, Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions . Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far.…”

“…27,52,53 Most Pb ions in circulation are carried by erythrocytes, and Pb transports into erythrocytes through sulfhydryl groups and the anion channel in the form of anionic complexes with carbonate, bicarbonate, hydroxyl, or chloride ions. 54 Regarding the molecular mechanisms of Pb-induced anemia, they are poorly understood, and only a few theories have been developed thus far. For example, the binding of Pb 2+ to protein sulfydryl groups would result in inhibition of ALA-D activity, leading to heme deficiency, and reduction of heme supply is a known reason for lead-related pathology.…”

Heavy Metals Affect Nematocysts Discharge Response and Biological Activity of Crude Venom in the JellyfishPelagia noctiluca(Cnidaria, Scyphozoa)

“…On a cellular level, the interaction of heavy metals with cell membrane transport mechanisms is the basis for their effect on biological systems. Examples of this interaction are given by Foulkes [50], describing the internalization of metals inside the cell, and Yu et al [51], describing an alteration of the activity of epithelial sodium channels (ENaC) following divalent heavy metals exposure.…”

“…In this regard, the latter authors reported that the mechanism of toxin action mainly depends on pore-forming into the membrane of cell target rather than oxidative damage, since GSH, cysteine and ascorbic acid did not impair the hemolytic power. Based on these observations, an intriguing hypothesis is that the interaction of metals with cell membrane [50] or crude venom components may reduce the hemolytic activity of venom by impairing the binding and insertion of pore-forming toxins in the membrane of target cells. Accordingly, Miyake et al [62] explained the inhibitory effect of divalent cations upon Vibrio metschnikovii cytolysin by changes in the erythrocytes membrane fluidity, so that pore formation due to the toxin was impaired, while, on the other hand, Iwase et al [63] suggested that extracellular Ca 2+ may accelerate the rate of removal of the toxin by endocytosis.…”