Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1993 Nov;101(6):510–516. doi: 10.1289/ehp.93101510

Electrical and freeze-fracture analysis of the effects of ionic cadmium on cell membranes of human proximal tubule cells.

D J Hazen-Martin 1, J H Todd 1, M A Sens 1, W Khan 1, J E Bylander 1, B J Smyth 1, D A Sens 1
PMCID: PMC1519902  PMID: 8137780

Abstract

We previously reported that cell cultures of human proximal tubule (HPT) cells respond to ionic cadmium in a manner consistent with well-defined Cd(2+)-elicited responses reported for in vivo systems. However, one unique finding was that the transepithelial electrical resistance and tight junction sealing strands were altered as a result of Cd2+ exposure at micromolar concentrations. These alterations are reexamined in detail in the present report to determine whether the Cd(2+)-induced alterations are specific alterations in the tight junction structure or reflect a general alteration in the cell membrane. Exhaustive analysis of tight junction sealing strands demonstrated no significant alterations due to Cd2+ exposure, even at the concentration that elicited a significant reduction in transepithelial resistance. Further analysis of intramembrane particle distribution demonstrated a significant increase in apical intramembrane particles, indicating that Cd2+ exposure altered the characteristics of the apical cell membrane. Overall, the results were consistent with evidence of Cd(2+)-induced alteration in the apical cell membrane of the HPT cell.

Full text

PDF
510

Images in this article

512Figure 1.
on p.512
512Figure 2.
on p.512
513Figure 3. a
on p.513
513Figure 3. b
on p.513
513Figure 3. c
on p.513
513Figure 3. d
on p.513
514Figure 4.
on p.514
514Figure 5.
on p.514

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blackburn J. G., Hazen-Martin D. J., Detrisac C. J., Sens D. A. Electrophysiology and ultrastructure of cultured human proximal tubule cells. Kidney Int. 1988 Feb;33(2):508–516. doi: 10.1038/ki.1988.27. [DOI] [PubMed] [Google Scholar]
  2. Detrisac C. J., Sens M. A., Garvin A. J., Spicer S. S., Sens D. A. Tissue culture of human kidney epithelial cells of proximal tubule origin. Kidney Int. 1984 Feb;25(2):383–390. doi: 10.1038/ki.1984.28. [DOI] [PubMed] [Google Scholar]
  3. Felley-Bosco E., Diezi J. Cadmium uptake and induction of metallothionein synthesis in a renal epithelial cell line (LLC-PK1). Arch Toxicol. 1991;65(2):160–163. doi: 10.1007/BF02034945. [DOI] [PubMed] [Google Scholar]
  4. Flath M. C., Bylander J. E., Sens D. A. Variation in sorbitol accumulation and polyol-pathway activity in cultured human proximal tubule cells. Diabetes. 1992 Sep;41(9):1050–1055. doi: 10.2337/diab.41.9.1050. [DOI] [PubMed] [Google Scholar]
  5. Forbush B., 3rd Assay of Na,K-ATPase in plasma membrane preparations: increasing the permeability of membrane vesicles using sodium dodecyl sulfate buffered with bovine serum albumin. Anal Biochem. 1983 Jan;128(1):159–163. doi: 10.1016/0003-2697(83)90356-1. [DOI] [PubMed] [Google Scholar]
  6. Hazen-Martin D. J., Sens D. A., Blackburn J. G., Flath M. C., Sens M. A. An electrophysiological freeze fracture assessment of cadmium nephrotoxicity in vitro. In Vitro Cell Dev Biol. 1989 Sep;25(9):791–799. doi: 10.1007/BF02623662. [DOI] [PubMed] [Google Scholar]
  7. Hazen-Martin D. J., Sens D. A., Blackburn J. G., Sens M. A. Cadmium nephrotoxicity in human proximal tubule cell cultures. In Vitro Cell Dev Biol. 1989 Sep;25(9):784–790. doi: 10.1007/BF02623661. [DOI] [PubMed] [Google Scholar]
  8. Janecki A., Jakubowiak A., Steinberger A. Effect of cadmium chloride on transepithelial electrical resistance of Sertoli cell monolayers in two-compartment cultures--a new model for toxicological investigations of the "blood-testis" barrier in vitro. Toxicol Appl Pharmacol. 1992 Jan;112(1):51–57. doi: 10.1016/0041-008x(92)90278-z. [DOI] [PubMed] [Google Scholar]
  9. Johnson J. P., Jones D., Wiesmann W. P. Hormonal regulation of Na+-K+-ATPase in cultured epithelial cells. Am J Physiol. 1986 Aug;251(2 Pt 1):C186–C190. doi: 10.1152/ajpcell.1986.251.2.C186. [DOI] [PubMed] [Google Scholar]
  10. Mandel L. J., Bacallao R., Zampighi G. Uncoupling of the molecular 'fence' and paracellular 'gate' functions in epithelial tight junctions. Nature. 1993 Feb 11;361(6412):552–555. doi: 10.1038/361552a0. [DOI] [PubMed] [Google Scholar]
  11. Middleton J. P., Dunham C. B., Onorato J. J., Sens D. A., Dennis V. W. Protein kinase A, cytosolic calcium, and phosphate uptake in human proximal renal cells. Am J Physiol. 1989 Oct;257(4 Pt 2):F631–F638. doi: 10.1152/ajprenal.1989.257.4.F631. [DOI] [PubMed] [Google Scholar]
  12. Palant C. E., Duffey M. E., Mookerjee B. K., Ho S., Bentzel C. J. Ca2+ regulation of tight-junction permeability and structure in Necturus gallbladder. Am J Physiol. 1983 Sep;245(3):C203–C212. doi: 10.1152/ajpcell.1983.245.3.C203. [DOI] [PubMed] [Google Scholar]
  13. Prozialeck W. C., Niewenhuis R. J. Cadmium (Cd2+) disrupts Ca(2+)-dependent cell-cell junctions and alters the pattern of E-cadherin immunofluorescence in LLC-PK1 cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1118–1124. doi: 10.1016/0006-291x(91)92054-n. [DOI] [PubMed] [Google Scholar]
  14. Prozialeck W. C., Niewenhuis R. J. Cadmium (Cd2+) disrupts intercellular junctions and actin filaments in LLC-PK1 cells. Toxicol Appl Pharmacol. 1991 Jan;107(1):81–97. doi: 10.1016/0041-008x(91)90333-a. [DOI] [PubMed] [Google Scholar]
  15. Todd J. H., Sens D. A., Sens M. A., Hazen-Martin D. In situ freeze-fracture of monolayer cell cultures grown on a permeable support. Microsc Res Tech. 1992 Aug 1;22(3):301–305. doi: 10.1002/jemt.1070220308. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES