Cadmium uptake through the anion exchanger in human red blood cells.

Lou, Manuel; Garay, Ricardo P.; Alda, J. O.

doi:10.1113/jphysiol.1991.sp018826

Cited by 53 publications

(27 citation statements)

References 24 publications

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“…It was suggested that anionic complexes formed between copper and anions (especially chloride) were transported as surrogate substrates by the anion exchange system (1). Such a mechanism has also been reported for the uptake of lead (38,39), zinc (23), and cadmium (30) in human red blood cells. This suggests that these anion transporters may play a hitherto unexpected role in metal homeostasis in humans (see below).…”

Section: Discussionmentioning

confidence: 91%

Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake

Zimnicka

Ivy

Kaplan

2011

American Journal of Physiology-Cell Physiology

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Copper is an essential micronutrient in humans and is required for a wide range of physiological processes, including neurotransmitter biosynthesis, oxidative metabolism, protection against reactive oxygen species, and angiogenesis. The first step in the acquisition of dietary copper is absorption from the intestinal lumen. The major human high-affinity copper uptake protein, human copper transporter hCTR1, was recently shown to be at the basolateral or blood side of both intestinal and renal epithelial cell lines and thus does not play a direct role in this initial step. We sought to functionally identify the major transport pathways available for the absorption of dietary copper across the apical intestinal membrane using Caco2 cells, a well-established model for human enterocytes. The initial rate of apical copper uptake into confluent monolayers of Caco2 cells is greatly elevated if amino acids and serum proteins are removed from the growth media. Uptake from buffered saline solutions at neutral pH (but not at lower pH) is inhibited by either d- or l-histidine, unaltered by the removal of sodium ions, and inhibited by ∼90% when chloride ions are replaced by gluconate or sulfate. Chloride-dependent copper uptake occurs with Cu(II) or Cu(I), although Cu(I) uptake is not inhibited by histidine, nor by silver ions. A well-characterized inhibitor of anion exchange systems, DIDS, inhibited apical copper uptake by 60–70%, while the addition of Mn(II) or Fe(II), competitive substrates for the divalent metal transporter DMT1, had no effect on copper uptake. We propose that anion exchangers play an unexpected role in copper absorption, utilizing copper-chloride complexes as pseudo-substrates. This pathway is also observed in mouse embryonic fibroblasts, human embryonic kidney cells, and Cos-7 cells. The special environment of low pH, low concentration of protein, and protonation of amino acids in the early intestinal lumen make this pathway especially important in dietary copper acquisition.

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Section: Discussionmentioning

confidence: 91%

Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake

Zimnicka

Ivy

Kaplan

2011

American Journal of Physiology-Cell Physiology

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“…This is in marked contrast to the results obtained for high-affinity uptake. Two anionic mechanisms of Zn¥ and Cd¥ transport into human erythrocytes have been described previously, requiring bicarbonate plus chloride and thiocyanate (or salicylate), respectively (Alda Torrubia & Garay, 1989;Lou et al 1991). The present investigation shows that similar transport processes are also present in rabbit erythroid cells and that transport mediated by bicarbonate plus chloride and by thiocyanate shows greater activity in mature erythrocytes than in reticulocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Effect of bicarbonate and thiocyanate on metal uptake Both HCO×¦ and SCN¦ have been reported to stimulate Zn¥ uptake (Alda Torrubia & Garay, 1989) and HCO×¦ to stimulate Cd¥ uptake (Lou, Garay & Alda Torrubia, 1991) by human erythrocytes. The effects of these anions on the Transition metal transport in erythroid cells Table 3.…”

Section: Competition For Metal Transportmentioning

confidence: 99%

Transport mechanisms for iron and other transition metals in rat and rabbit erythroid cells

Savigni

Morgan

1998

The Journal of Physiology

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Earlier studies have shown that Fe2+ transport into erythroid cells is inhibited by several transition metals (Mn2+, Zn2+, Co2+, Ni2+) and that Fe2+ transport can occur by two saturable mechanisms, one of high affinity and the other of low affinity. Also, the transport of Zn2+ and Cd2+ into erythroid cells is stimulated by NaHCO3 and NaSCN. The aim of the present investigation was to determine whether all of these transition metals can be transported by the processes described for Fe2+, Zn2+ and Cd2+ and to determine the properties of the transport processes. Rabbit reticulocytes and mature erythrocytes and reticulocytes from homozygous and heterozygous Belgrade rats were incubated with radiolabelled samples of the metals under conditions known to be optimal for high‐ and low‐affinity Fe2+ transport and for the processes mediated by NaHCO3 and NaSCN. All of the metals were transported by the high‐ and low‐affinity Fe2+ transport processes and could compete with each other for transport. The Km and Vmax values and the effects of incubation temperature and metabolic inhibitors were similar for all the metals. NaHCO3 and NaSCN increased the uptake of Zn2+ and Cd2+ but not the other metals. The uptake of all of the metals by the high‐affinity process was much lower in reticulocytes from homozygous Belgrade rats than in those from heterozygous animals, but there was no difference with respect to low‐affinity transport. It is concluded that the high‐ and low‐affinity ‘iron’ transport mechanisms can also transport several other transition metals and should therefore be considered as general transition metal carriers.

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“…In addition, Zn (Alda & Garay 1989;Kalfakakou & Simons 1990), Cu (Alda & Garay 1990), and Pb (Simons 1986) were reported to be taken up by red blood cells via the anion exchanger, and Kalfakakou & Sinions (1990) suggested the competitive inhibitory effect of Zn on Pb uptake by the cells. These investigators (Alda & Garay 1989& 1990Lou et al 1991) implied the contribution of the inorganic anion exchanger in the renal reabsorption of these metals, however, this point had not yet been investigated. Simons (1986) provided evidence for the involvement of a carrier-mediated process in Pb uptake in human red blood cell membrane by incubation of the cell membrane with Pb at different temperatures.…”

mentioning

confidence: 99%

Cadmium Uptake from Apical Membrane of LLC–PK Cells via Inorganic Anion Exchanger

Endo

Kimura

Sakata

1998

Pharmacology & Toxicology

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ilbsrrtrci; Effects of Na+, CI-, OH-and HCO,-, and an inorganic tinion exchange inhibitor (HCO, iC1 ), 4,4'-diisothiocyanostilbcne-2,2'-disulfonic acid, on Cd uptake from the apical membrane of LLC-PK I cells were investigated to elucidate the mechanism of Cd uptake by thcsc cells. Furthermore, the initial uptake of Cd incubated at different temperatures was analyLed by using the Arrhcnius plot to tcst if Cd is taken up by the cells via the carrier-mediated process. The cells were incubated with 1 pM CdClz for 30 min. at 37" in phosphate buffer containing NaCl at pH 5.5 or 7.4. Cd accumulation by the cclls at pH 7.4 was about 5 times higher than at pH 5.5. Rcplaccmcnt of NaCl in the phosphate buffer with KCI or niannitol dccrcased the Cd accumulation at pH 7.4 about 80%, but had no effect at pH 5.5. The addition of 2 mM NaHCOl to the pH 7.4 buffer containing NaCl significantly increased the Cd accurnulation, and pretreatment of the cells with the inorganic anion exchange inhibitor abolished this effect of NaHCOl on Cd accumulation. The cells were incubated for 10 min. at different temperatures with 1 pM CdClz in the phosphate buffer containing NaCl at pH 7.4 in the presence or absence of 2 mM NaHCO3 or at pH 5.5 in the absence of NaHCOl. In all cases, the Arrhenius plots of Cd accumulation were nonlinear. The breakpoint was observed at about 30" in thc Cd accumulation at pH 7.4 in the presence of NaIICO,, suggesting the involvement of a carrier-mediated process. This brcakpoirit was not as clear in the Cd accumulation at pH 7.4 in the absence of NaHCO3 and not observed at all at pH 5.5. These findings suggested that Cd is partially taken up from the apical membrane of LLC-PKI cells via the inorganic anion exchanger and the uptake of Cd is more efficient a t alkaline pH and in the presence of Na+, C1-and HCO, .We studied the mechanism of uptake of CdClz by LLC-PKI cells, iin established renal tubular epithelial cell line and brush border metnbranc vesicles isolated from rat renal cortex. Cd appears to be partially taken up from the apical membrane of LLC-PK I cells via a carrier-mediated system involving tcmpcrature-, N a~' -, energy-, and pH-dependent process(es) when the cells were incubated with non

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Cadmium uptake through the anion exchanger in human red blood cells.

Cited by 53 publications

References 24 publications

Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake

Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake

Transport mechanisms for iron and other transition metals in rat and rabbit erythroid cells

Cadmium Uptake from Apical Membrane of LLC–PK Cells via Inorganic Anion Exchanger

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