Localisation of oxysterols at the sub-cellular level and in biological fluids. Issue 193 (October 2019)

• Record Type: Journal Article
• Authors: Dias, Irundika HK; Borah, Khushboo; Amin, Berivan; Griffiths, Helen R.; Sassi, Khouloud; Lizard, Gérard; Iriondo, Ane; Martinez-Lage, Pablo
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 193(2019)
• Publication Date: 2019-10
• Subjects: 20-OHC 20-hydroxycholesterol -- 22-OHC 22-hydroxycholesterol -- 24-OHC 24-hydroxycholesterol -- 25-OHC 25-hydroxycholesterol -- 26-OHC 26-hydroxycholesterol -- 27-OHC 27-hydroxycholesterol -- 5, 6-epox 5, 6-epoxy cholesterols -- 5α, 6α-epox 5α, 6α- epoxy cholesterol -- 5β, 6β-epox 5β, 6β- epoxy cholesterol -- 7-KC 7-ketocholesterol -- 7-K, 25-OHC 7-keto-27-hydroxycholesterol -- 7α-OHC 7α-hydroxycholesterol -- 7α, 25-OHC 7α, 25-dihydroxycholesterol -- 7α, 27-OHC 7α, 27-hydroxycholesterol -- 7β-OHC 7β-hydroxycholesterol -- ABCA1 ATP-binding cassette transporter A1 -- ABCG1 aTP-binding cassette transporter G1 -- ACAT acyl-CoA:cholesterol acyl transferase -- AD alzheimer´s disease -- APP amyloid precursor protein -- BBB blood-brain barrier -- CH25H cholesterol 25-hydroxylase -- ChEH cholesterol-5, 6-epoxide hydrolase -- CNBP cellular nucleic acid binding protein -- CYP46A1 cholesterol 24-hydroxylase -- CYP46A1 cytochrome P450 46A1 -- CYP7A1 Sterol 7α-hydroxylase -- CYP27 Sterol 27-hydroxylase -- CYP8B1 cholesterol 12α‐hydroxylase -- DDA Dendrogenin A -- DHCA dihydroxycholestanoic acid -- ER endoplasmic reticulum -- HSD hydroxysteroid dehydrogenase -- HSD3B7 3β-hydroxysteroid dehydrogenase type 7 -- LDL low density lipoproteins -- LXR liver X receptor -- MS multiple sclerosis -- NAFLD non-alcoholic fatty liver disease -- OSBP oxysterol binding protein -- PD Parkinson´s disease -- POPC 1-palmitoyl-2-oleoyl-phosphatidylcholine -- SCAP SREBP cleavage activation protein -- SMO smoothed receptor -- SREBP sterol regulatory element binding protein -- StAR steroidogenic acute regulatory protein -- THCA trihydroxycholestanoic acid -- TSPO mitochondrial translocator protein -- ROS reactive oxygen species -- VLCFA very long chain fatty acids -- WMH white matter hyperintensitiess; Oxysterols -- Subcellular -- Membrane -- Mitochondria -- Peroxisomes -- Fluids; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2019.105426
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Oxysterols are involved in many biological processes including the regulation of cholesterol homeostasis. The location of oxysterol metabolising enzymes may play an important role in cellular oxysterol concentration. Oxysterols in biological fluids can use as markers to analyse endogenous flaws in cholesterol/oxysterol homeostasis. Abstract: Oxysterols are oxidized derivatives of cholesterol that are formed enzymatically or via reactive oxygen species or both. Cholesterol or oxysterols ingested as food are absorbed and packed into lipoproteins that are taken up by hepatic cells. Within hepatic cells, excess cholesterol is metabolised to form bile acids. The endoplasmic reticulum acts as the main organelle in the bile acid synthesis pathway. Metabolised sterols originating from this pathway are distributed within other organelles and in the cell membrane. The alterations to membrane oxysterol:sterol ratio affects the integrity of the cell membrane. The presence of oxysterols changes membrane fluidity and receptor orientation. It is well documented that hydroxylase enzymes located in mitochondria facilitate oxysterol production via an acidic pathway. More recently, the presence of oxysterols was also reported in lysosomes. Peroxisomal deficiencies favour intracellular oxysterols accumulation. Despite the low abundance of oxysterols compared to cholesterol, the biological actions of oxysterols are numerous and important. Oxysterol levels are implicated in the pathogenesis of multiple diseases ranging from chronic inflammatory diseases (atherosclerosis, Alzheimer's disease and bowel disease), cancer and numerous neurodegenerative diseases. In this article, we review the distribution of oxysterols in sub-cellular organelles and in biological fluids.