THP1 macrophages oxidized cholesterol, generating 7-derivative oxysterols specifically released by HDL

Autor: Michel Lagarde, Isabelle Delton, Celine Luquain-Costaz, Maud Arnal-Levron, Yinan Chen, Philippe Moulin
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Department of Endocrinology, Hôpitaux Est Hôpital Louis Pradel - Hospices Civils de Lyon, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Endosomes/drug effects/metabolism
HDL/*metabolism
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Intracellular Space
LDL/metabolism
Androstenes/pharmacology
medicine.disease_cause
Biochemistry
chemistry.chemical_compound
Mice
Endocrinology
polycyclic compounds
Cytotoxicity
Ketocholesterols
Cells
Cultured
Cultured
Intracellular Space/metabolism
Lipoproteins
LDL
Cholesterol
Low-density lipoprotein
Androstenes
lipids (amino acids
peptides
and proteins)
Cholesterol/*metabolism
Efflux
Lipoproteins
HDL
Oxidation-Reduction
Intracellular
Oxysterol
Endosome
Cells
Lipoproteins
Endosomes
Apolipoprotein A-I/metabolism
Oxidation-Reduction/drug effects
medicine
Animals
Humans
Molecular Biology
Pharmacology
Apolipoprotein A-I
Macrophages
Organic Chemistry
Macrophages/drug effects/*metabolism
RAW 264.7 Cells
chemistry
Ketocholesterols/*metabolism
Oxidative stress
Zdroj: Steroids
Steroids, Elsevier, 2015, 99 (Pt B), pp.212-8. ⟨10.1016/j.steroids.2015.02.020⟩
ISSN: 0039-128X
DOI: 10.1016/j.steroids.2015.02.020⟩
Popis: International audience; Macrophages are well recognized as key pathophysiologic agents in many chronic inflammatory diseases, especially atherosclerosis. During atherogenesis process, low density lipoproteins (LDL) undergo oxidation (oxLDL) and become highly atherogenic as they induce a strong accumulation of cholesterol in subendothelial macrophages leading to the formation of foam cells, the major cellular component of fatty streaks. OxLDL are enriched in oxidation products of cholesterol called oxysterols involved in the regulation of cholesterol homeostasis, by their ability to induce cellular oxidative stress and cytotoxicity. Little is known about intracellular oxysterol production in macrophages. Using both radiochemical and mass analyzes, we showed that THP1 macrophages promote the intracellular oxidation of LDL derived-cholesterol as well as intracellular cholesterol, this later mechanism being enhanced by exposure with native or oxLDL. We demonstrated that in both THP1 and Raw 267.4 cells cholesterol oxidation occurs in the late endosomal compartment. Most oxysterols were produced by non-enzymatic routes (7-ketocholesterol and 7alpha/beta-hydroxycholesterol) but enzymatically formed 7alpha-, 27-hydroxycholesterol were also quantified. Incubation of THP1 macrophages with nLDL or oxLDL, induced a 2- and 100-fold increase in oxysterol production, respectively. Both oxysterols derived from LDL cholesterol and cellular cholesterol were readily exported to HDL whereas apoA1 was inefficient, showing that HDL plays a major role in the removal of excess oxysterols in THP1 macrophages.
Databáze: OpenAIRE
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