How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect on the partitioning of CE between HDL and the water phase. However, BODIPY-CE was observed to diffuse more slowly and locate itself closer to the HDL-water interface than CE due to the BODIPY probe that is constrained to the surface region, and because the CE body in BODIPY-CE prefers to align itself away from the HDL surface. The implications as to the suitability of BODIPY to explore lipoprotein properties are discussed

Differences in acute cytotoxicity between organic chemicals with and without C₆₀.

<p>C₆₀ was mixed overnight with and without organic chemicals in cRPMI medium containing 2% BSA before a 24 h exposure to the cells. Cytotoxicity was measured by LDH release compared to the positive control. Three unfiltered (A) and two filtered (B) samples were studied.</p

Co-Exposure with Fullerene May Strengthen Health Effects of Organic Industrial Chemicals

<div><p><i>In vitro</i> toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C₆₀ fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, <i>m</i>-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C₆₀ and organic chemicals represent different co-exposure scenarios in <i>in vitro</i> studies where acute cytotoxicity and immunotoxicity of C₆₀ and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C₆₀ that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of <i>m</i>-cresol and C₆₀ that is slightly less cytotoxic than <i>m</i>-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1β and TNF-α is considered. Complementary atomistic molecular dynamics simulations reveal that C₆₀ co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C₆₀ molecules aggregate together, a portion of organic molecules remains in water.</p></div

TEM images of human THP-1-derived macrophages.

<p>The cells were exposed to unfiltered suspensions of pure C₆₀ (A) and C₆₀ with acetophenone (B), benzaldehyde (C), benzyl alcohol (D), <i>m</i>-cresol (E), and toluene (F). Black deposits inside the cells represent aggregates of C₆₀.</p

Correlation of C₆₀-induced changes in secretion of pro-inflammatory cytokine IL-1β and partitioning of organic molecules.

<p>Correlations were determined for unfiltered (A, C, E) and filtered (B, D, F) samples, considering the partitioning of organic molecules in cluster core (A, B), cluster surface (C, D), and solvent (E, F) in the simulated mixtures.</p

Intensity average diameters and ζ-potentials of C₆₀ aggregates in suspensions filtered through a 0.45 µm filter.

<p>Intensity average diameters and ζ-potentials of C₆₀ aggregates in suspensions filtered through a 0.45 µm filter.</p

Change in free energy (Δ<i>G</i>) during the translocation of a single C₆₀ molecule.

<p>Translocation is followed from the center of the cluster to the water phase along a radial distance <i>r</i>. The clusters are divided into various parts according to the RDF data. In the pure C₆₀ cluster, the interface is where C₆₀ and water are in contact.</p

Final structures of C₆₀ clusters with and without organic molecules.

<p>We use a color scheme for fullerene (gray), organic molecules (cyan/white/red for carbon/hydrogen/oxygen, respectively), and water (red/white). Pure C₆₀ (A), spherical cluster of pure C₆₀ for umbrella sampling (B), C₆₀/acetophenone (C), C₆₀/acetophenone cross-section (D), C₆₀/benzaldehyde (E), C₆₀/benzaldehyde cross-section (F), C₆₀/benzyl alcohol (G), C₆₀/benzyl alcohol cross-section (H), C₆₀/<i>m</i>-cresol (I), C₆₀/<i>m</i>-cresol cross-section (J), C₆₀/toluene (K), and C₆₀/toluene cross-section (L).</p

Relative differences in immunotoxicity between organic chemicals with and without C₆₀.

<p>C₆₀ was mixed overnight with and without organic chemicals in cRPMI medium containing 2% BSA before a 24 h exposure to the cells. Immunotoxicity was determined by measuring secretion of pro-inflammatory cytokines IL-1β (A, B) and TNF-α (C, D). Two unfiltered (A, C) and two filtered (B, D) samples were studied.</p