The stress response of human proximal tubule cells to cadmium involves up-regulation of haemoxygenase 1 and metallothionein but not cytochrome P450 enzymes

Boonprasert, Kanyarat, Satarug, Soisungwan, Morais, Christudas, Gobe, Glenda C., Johnson, David W., Na-Bangchang, Kesara and Vesey, David A. (2016) The stress response of human proximal tubule cells to cadmium involves up-regulation of haemoxygenase 1 and metallothionein but not cytochrome P450 enzymes. Toxicology Letters, 249 5-14. doi:10.1016/j.toxlet.2016.02.016


Author Boonprasert, Kanyarat
Satarug, Soisungwan
Morais, Christudas
Gobe, Glenda C.
Johnson, David W.
Na-Bangchang, Kesara
Vesey, David A.
Title The stress response of human proximal tubule cells to cadmium involves up-regulation of haemoxygenase 1 and metallothionein but not cytochrome P450 enzymes
Journal name Toxicology Letters   Check publisher's open access policy
ISSN 1879-3169
0378-4274
Publication date 2016-05-13
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.toxlet.2016.02.016
Open Access Status Not Open Access
Volume 249
Start page 5
End page 14
Total pages 10
Place of publication Shannon, Clare Ireland
Publisher Elsevier Ireland
Collection year 2017
Language eng
Abstract Enzymes of the cytochrome P450 (CYP) super-family are implicated in cadmium (Cd) -induced nephrotoxicity, however, direct evidence is lacking. This study investigated the endogenous expression of various CYP proteins together with the stress-response proteins, heme oxygenase-1 (HO-1) and metallothionein (MT) in human kidney sections and in cadmium-exposed primary cultures of human proximal tubular epithelial cells (PTC). By immunohistochemistry, the CYP members 2B6, 4A11 and 4F2 were prominently expressed in the cortical proximal tubular cells and to a lesser extent in distal tubular cells. Low levels of CYPs 2E1 and 3A4 were also detected. In PTC, in the absence of Cd, CYP2E1, CYP3A4, CYP4F2 and MT were expressed, but HO-1, CYP2B6 and CYP4A11 were not detected. A range of cadmium concentrations (0-100 μM) were utilized to induce stress conditions. MT protein was further induced by as little as 0.5 μM cadmium, reaching a 6-fold induction at 20 μM, whereas for HO-1, a 5 μM cadmium concentration was required for initial induction and at 20 μM cadmium reached a 15-fold induction. The expression of CYP2E1, CYP3A4, and CYP4F2 were not altered by any cadmium concentrations tested at 48 h. Cadmium caused a reduction in cell viability at concentrations above 10 μM. In conclusion although cultured PTC, do express CYP proteins, (CYP2E1, CYP3A4, and CYP4F2), Cd-induced cell stress as indicted by induction of HO-1 and MT does not alter expression of these CYP proteins at 48 h.
Keyword Cadmium
Cytochrome P450 (CYP)
Drug-metabolizing enzymes
Heme oxygenase-1
HK2 cells
Metallothionein
Proximal tubular cells
Stress response
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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