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Titolo:
Transferrin-mediated uptake of aluminium by human parathyroid cells results in reduced parathyroid hormone secretion
Autore:
Smans, KA; DHaese, PC; Van Landeghem, GF; Andries, LJ; Lamberts, LV; Hendy, GN; De Broe, ME;
Indirizzi:
Univ Antwerp, Dept Physiol, B-2020 Antwerp, Belgium Univ Antwerp AntwerpBelgium B-2020 ept Physiol, B-2020 Antwerp, Belgium Univ Antwerp, Dept Nephrol, B-2020 Antwerp, Belgium Univ Antwerp AntwerpBelgium B-2020 ept Nephrol, B-2020 Antwerp, Belgium Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada Royal Victoria Hosp Montreal PQ Canada H3A 1A1 ntreal, PQ H3A 1A1, Canada
Titolo Testata:
NEPHROLOGY DIALYSIS TRANSPLANTATION
fascicolo: 9, volume: 15, anno: 2000,
pagine: 1328 - 1336
SICI:
0931-0509(200009)15:9<1328:TUOABH>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADYNAMIC BONE-DISEASE; RENAL OSTEODYSTROPHY; DIALYSIS PATIENTS; IRON; HYPERPARATHYROIDISM; MECHANISM; INVITRO; THERAPY; SERUM; GENE;
Keywords:
adynamic bone disease; aluminium-citrate; aluminium-transferrin; human parathyroid cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: De Broe, ME Univ Antwerp, Univ Antwerp Hosp, Dept Nephrol Hypertens, Wilrijkstr 10, B-2650 Edegem, Belgium Univ Antwerp Wilrijkstr 10 Edegem BelgiumB-2650 gem, Belgium
Citazione:
K.A. Smans et al., "Transferrin-mediated uptake of aluminium by human parathyroid cells results in reduced parathyroid hormone secretion", NEPH DIAL T, 15(9), 2000, pp. 1328-1336

Abstract

Background. The present study investigates whether aluminium-transferrin (Al-Tf) uptake by Tf receptor-mediated endocytosis induces hypoparathyroidism and thus might contribute to the increasing prevalence of adynamic bone disease (ABD) in the current dialysis population. Methods and Results. Human parathyroid glands as well as in vitro culturedhuman parathyroid cells were shown to express Tf receptors. Five-day-old cultures of parathyroid cells were incubated for 48 h in serum-free DMEM/F12supplemented with 12 mu M apo-Tf: 12 mu M Tf to which 150 mu g/l Al or 150mu g/l Al-citrate (Al-ci) was bound. The amount of Al taken up by the parathyroid cells either as Al-Tf or Al-ci did not differ. However, incubation of cell cultures with Al-Tf showed a significant proportional decrease (mean+/-SEM, -23.1+/-4.5%) in iPTH secretion as compared to the reference apo-Tf cultures. Al-ci did not suppress PTH secretion (+3.4+/-6.5%). The Al uptake after incubation with Al-Tf was found to be dose-dependent. With regard to iPTH secretion, a tendency toward a dose response relationship was observed. Northern blot analysis of parathyroid cells incubated in 12 mu M apo-Tf or 12 mu M Al-Tf demonstrated that the PTH mRNA synthesis was unaffected by the Tf-mediated uptake of Al. These observations suggest an effect of Alon PTH release rather than on PTH synthesis. Since the cytoskeleton can play an important role in the release of secretory vesicles, the influence ofAl on the structure of actin, beta-tubulin and vimentin was investigated by confocal microscopy. Comparison of cultures incubated with apo-Tf and Al-TF revealed no difference in the organization of these cytoskeletal proteins in relation to the inhibitory effect of Al-Tf on PTH secretion. Conclusion. In summary, data in the present paper demonstrate that the (i)human parathyroid gland/parathyroid cells exhibit Tf receptors; (ii) Al-Tfcomplex is taken up by the parathyroid gland in a dose-dependent manner; and (iii) uptake of Al by Tf receptor-mediated endocytosis reduces the secretion of PTH but not its synthesis. These in vitro findings allow us to suggest that Tf receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaCO3 intake, play a role in the development of hypoparathyroidism associated with ABD. The exact mechanism by which Al-Tf suppresses iPTH secretion remains to be elucidated.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 19:57:49