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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Pfeifer, T; Buchebner, M; Chandak, PG; Patankar, J; Kratzer, A; Obrowsky, S; Rechberger, GN; Kadam, RS; Kompella, UB; Kostner, GM; Kratky, D; Levak-Frank, S.
Synthetic LXR agonist suppresses endogenous cholesterol biosynthesis and efficiently lowers plasma cholesterol.
Curr Pharm Biotechnol. 2011; 12(2):285-292 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText

 

Autor/innen der Med Uni Graz:
Chandak Prakash Gopal Das
Kostner Gerhard
Kratky Dagmar
Levak Sanja
Obrowsky Sascha
Patankar Jay Vasant
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Number of Figures: 6
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Abstract:
The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid disorders. N,N-dimethyl-3β-hydroxycholenamide (DMHCA) is a steroidal ligand of LXRs that exerts anti-atherogenic effects in apolipoprotein E-deficient mice without causing negative side effects such as liver steatosis or hypertriglyceridemia. In this report, we investigated the consequences of DMHCA treatment on cholesterol homeostasis in vivo and in vitro. Despite its hydrophobicity, DMHCA is readily absorbed by C57BL/6 mice and taken up by intestinal cells, the lung, heart and kidneys, but is undetectable in the brain. DMHCA significantly reduces cholesterol absorption and uptake in duodenum and jejunum of the small intestine and in turn leads to a reduction of plasma cholesterol by 24%. The most striking finding of this study is that DMHCA inhibited the enzyme 3β-hydroxysterol-Δ24-reductase resulting in an accumulation of desmosterol in the plasma and in feces. Thus, the reduction of plasma cholesterol was due to a block in the final step of cholesterol biosynthesis. Taken together, DMHCA is an interesting compound with properties distinct from other LXR ligands and might be used to study desmosterol-mediated effects in cells and tissues.
Find related publications in this database (using NLM MeSH Indexing)
Androstenes - pharmacokinetics
Animals -
Anticholesteremic Agents - pharmacokinetics
Cell Survival - drug effects
Cholesterol - biosynthesis
Cholic Acids - pharmacokinetics
Desmosterol - metabolism
Enzyme Inhibitors - pharmacokinetics
Fatty Liver - chemically induced
Feces -
Hep G2 Cells -
Humans -
Intestines - drug effects
Lipid Metabolism - drug effects
Lipogenesis - drug effects
Male -
Mice -
Mice, Inbred C57BL -
Nerve Tissue Proteins - antagonists & inhibitors
Orphan Nuclear Receptors - agonists
Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors

Find related publications in this database (Keywords)
Cholesterol absorption
cholesterol biosynthesis
desmosterol
DHCR24
DMHCA
liver X receptor
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