Chlordecone increased subcellular distribution of scavenger receptor class B type II to murine hepatic microsomes without altering cytosolic cholesterol binding proteins.
Pretreatment of male C57BL/6 mice with low doses of the persistent organochlorine pesticide, chlordecone (CD), stimulated biliary excretion of exogenous cholesterol (CH) up to 3-fold. Increased biliary excretion occurred without changes in hepatic ATP-binding cassette transporter G8 (ABCG8) of the bile canaliculus or scavenger receptor class B type I (SR-BI) of the sinusoidal surface. A variety of tissues express scavenger receptor class B type II (SR-BII) and this protein was identified as a splice variant from the SR-BI gene. Although the function of SR-BII has not been elucidated it may play a role in CH homeostasis and trafficking distinctly different than SR-BI. Western blotting demonstrated that a single dose of CD promoted subcellular distribution of SR-BII to murine hepatic microsomes about 2.2-fold when compared to controls without effect on liver crude membrane SR-BII content. This was consistent with increased vesicular CH trafficking. Relative quantification of hepatic cytosolic proteins in a fraction that sequestered [(14)C]CH by mass spectrometry (MS) indicated no role for cytosolic CH binding proteins in CD altered CH homeostasis. Western blotting verified no effect of CD on liver fatty acid-binding protein (L-FABP) in cytosol. MS detected a statistically significant increase in myosin-9, which was also consistent with increased vesicular trafficking.
Scheri
Richard C
RC
Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Lee
Junga
J
Barofsky
Douglas F
DF
Curtis
Lawrence R
LR
D000818:Animals; D001646:Bile / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D007631:Chlordecone / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D010196:Pancreatic Elastase; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects* / Q000378:metabolism*
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D007306:Insecticides; D051122:Scavenger Receptors, Class B; D010196:Pancreatic Elastase; C017130:cholesterol-binding protein; D007631:Chlordecone