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Chlordecone Increased Subcellular Distribution of Scavenger Receptor Class B Type II to Murine Hepatic Microsomes without Altering Cytosolic Cholesterol Binding Proteins

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  • Pretreatment of male C57BL/6 mice with low doses of the persistent organochlorine (OC) pesticide, chlordecone (CD), stimulated biliary excretion of exogenous 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 [¹⁴C]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.
  • Keywords: Chlordecone, Scavenger receptor class B type II, Cholesterol
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  • Scheri, R. C., Lee, J., Barofsky, D. F., & Curtis, L. R. (2009). Chlordecone increased subcellular distribution of scavenger receptor class B type II to murine hepatic microsomes without altering cytosolic cholesterol binding proteins. Toxicology Letters, 191(1), 20-25. doi:10.1016/j.toxlet.2009.07.029
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  • 191
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  • 1
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