Single-Protein Tracking Reveals That NADPH Mediates the Insertion of Cytochrome P450 Reductase into a Biomimetic of the Endoplasmic Reticulum

2017 ◽  
Vol 139 (15) ◽  
pp. 5420-5430 ◽  
Author(s):  
Carlo Barnaba ◽  
Michael J. Martinez ◽  
Evan Taylor ◽  
Adam O. Barden ◽  
James A. Brozik
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome P450 ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Single Protein ◽  
Protein Tracking

scholarly journals Single Protein Tracking of P450-Reductase in an Endoplasmic Reticulum Biomimetic Reveals a NADPH Dependent Interaction with the Membrane

2017 ◽  
Vol 112 (3) ◽  
pp. 508a
Author(s):  
James A. Brozik ◽  
Carlo Barnaba ◽  
Adam O. Barden ◽  
Linda Agyen ◽  
Sean L. Sheridan
Keyword(s):  
Endoplasmic Reticulum ◽  
P450 Reductase ◽  
Single Protein ◽  
Protein Tracking ◽  
Dependent Interaction

Fatty Liver and Impaired Hepatic Metabolism Alters the Congener-Specific Distribution of Polychlorinated Biphenyls (PCBs) in Mice with a Liver-Specific Deletion of Cytochrome P450 Reductase

2020 ◽  
Author(s):  
Xueshu Li ◽  
Chun-Yun Zhang ◽  
Hans-Joachim Lehmler
Keyword(s):  
Cytochrome P450 ◽  
Polychlorinated Biphenyls ◽  
Fatty Liver ◽  
Partition Coefficients ◽  
Hepatic Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Specific Distribution ◽  
Specific Deletion

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are linked to adverse health outcomes. PCB tissue levels are determinants of PCB toxicity; however, it is unclear how factors, such as an altered metabolism and/or a fatty liver, affect PCB distribution in vivo. We determined the congener-specific disposition of PCBs in mice with a liver specific deletion of cytochrome P450 reductase (KO), a model of fatty liver with impaired hepatic metabolism, and wildtype (WT) mice. Male and female KO and WT mice were exposed orally to Aroclor 1254, a technical PCB mixture. PCBs were quantified in adipose, blood, brain and liver tissues by gas chromatography-mass spectrometry. PCB profiles and levels in tissues were genotype and sex dependent. PCB levels were higher in the liver from KO compared to WT mice. PCB profiles showed clear differences between tissues from the same exposure group. While experimental tissue : blood partition coefficients in KO and WT mice did not follow the trends predicted using a composition-based model, the agreement between experimental and calculated partition coefficients was still reasonable. Thus, a fatty liver and/or an impaired hepatic metabolism alter the distribution of PCBs in mice and the magnitude of the partitioning of PCBs from blood into tissues can be approximated using composition-based models.<br>

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