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conferenceseries
.com
Volume 8
Medicinal Chemistry
ISSN: 2161-0444
Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10
th
World Congress on
Medicinal Chemistry and Drug Design
Lyso-DGTS lipid isolated from microalgae enhances PON1 activities
in vitro
and
in vivo
, increases
PON1 penetration into macrophages and decreases cellular lipid accumulation
Soliman Khatib
1, 2
1
MIGAL–Galilee Research Institute, Israel
2
Tel-Hai College, Israel
H
igh-density lipoprotein (HDL) plays an important role in preventing atherosclerosis. The antioxidant effect of HDL is
mostly associated with paraoxonase 1 (PON1) activity. Increasing PON1 activity using nutrients might improve HDL
function and quality and thus, decrease atherosclerotic risk. We previously isolated and identified a novel active compound,
Lyso-DGTS (C20:5, 0) from
Nannochloropsis
sp. ethanol extract. In the present study, its effect on PON1 activities was
examined and the mechanism by which the compound affects PON1 activity was explored. Lyso-DGTS elevated recombinant
PON1 (rePON1) lactonase and esterase activities in a dose- and time-responsive manner, and further stabilized and preserved
rePON1 lactonase activity. Incubation of lyso-DGTS with human serum for 4 h at 37˚C also increased PON1 lactonase activity
in a dose-responsive manner. Using tryptophan-fluorescence-quenching assay, lyso-DGTS was found to interact with rePON1
spontaneously with negative free energy G=-22.87 KJ/mol at 25˚C). Thermodynamic parameters and molecular modeling
calculations showed that the main interaction of lyso-DGTS with the enzyme is through a hydrogen bond with supporting
van der Waals interactions. Furthermore, lyso-DGTS significantly increased rePON1 influx into macrophages and prevented
lipid accumulation in macrophages stimulated with oxidized low-density lipid dose-dependently.
In-vivo
supplementation
of lyso-DGTS to the circulation of mice fed a high-fat diet via osmotic mini-pumps implanted subcutaneously significantly
increased serum PON1 lactonase activity and decreased serum glucose concentrations to the level of mice fed a normal diet.
Our findings suggest a beneficial effect of lyso-DGTS on increasing PON1 activity and thus, improving HDL quality and
atherosclerotic risk factors.
solimankh@migal.org.ilMed chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-040