Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

TY - JOUR

T1 - Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

AU - Hjelmborg, Philip Sebastian

AU - Andreassen, Thomas Kjærgaard

AU - Bonefeld-Jørgensen, Eva Cecilie

PY - 2008

Y1 - 2008

N2 -  There are a number of interactions related to transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans.The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro.Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [14C]DDT uptake was inversely dependent on the LDL concentration. There was no strong evidence for a receptor mediated uptake of the [14C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway.

AB -  There are a number of interactions related to transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans.The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro.Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [14C]DDT uptake was inversely dependent on the LDL concentration. There was no strong evidence for a receptor mediated uptake of the [14C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway.

KW - LDL; POPs; MEF cells; receptor mediated uptake; ultracentrifugation.

U2 - 10.1016/j.envres.2008.07.019

DO - 10.1016/j.envres.2008.07.019

M3 - Journal article

C2 - 18762293

SN - 0013-9351

VL - 108

SP - 192

EP - 198

JO - Environmental Research

JF - Environmental Research

IS - 2

ER -