Changes in the function of angiotensin II type 1 receptor due to cholesterol depletion from cell membrane
Autor: | Yoshiaki Idemoto, Yoshino Matsuo, Shin-ichiro Miura, Takashi Kuwano, Yasunori Suematsu, Ken Kitajima |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Statin medicine.drug_class Inositol Phosphates Myocytes Smooth Muscle Biophysics Biochemistry Receptor Angiotensin Type 1 Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Chlorocebus aethiops Cyclic AMP medicine Animals Humans Myocytes Cardiac Receptor Inositol phosphate Molecular Biology G protein-coupled receptor chemistry.chemical_classification Oxadiazoles Angiotensin II receptor type 1 Cholesterol Angiotensin II Cell Membrane Cell Biology Rats HEK293 Cells 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry 030220 oncology & carcinogenesis COS Cells cardiovascular system Benzimidazoles hormones hormone substitutes and hormone antagonists |
Zdroj: | Biochemical and Biophysical Research Communications. 514:791-797 |
ISSN: | 0006-291X |
Popis: | Blockers of G-protein coupled receptors (GPCRs), angiotensin II (Ang II) type 1 (AT1) receptor and β1-adrenergic (Ad) receptor, have been shown to improve the prognosis of cardiovascular disease. Cholesterol molecules in the cell membrane are needed to stabilize GPCRs as well as the cell membrane itself. We determined whether the functions of AT1 and β1-Ad receptors were changed by cholesterol depletion from cardiovascular cell membranes. Ang II-induced inositol phosphate production through AT1 receptor was suppressed by cholesterol depletion from cell membranes using rosuvastatin or methyl-β-cyclodextrin (MβCD), whereas isoproterenol-induced cyclic AMP production through β1-Ad receptor did not change after cholesterol depletion. In addition, the binding affinities of Ang II and AT1 receptor blocker after cholesterol depletion were significantly lower than those before depletion. Although AT1 receptor expression levels did not change after cholesterol depletion, the expression levels of AT1 receptor that could bind to Ang II significantly decreased after depletion. The changes in the structure of AT1 receptor due to depletion were confirmed by substituted-cysteine accessibility mapping. In conclusion, Ang II-induced activation of AT1 receptor is reduced without affecting the function of β1-Ad receptor after cholesterol depletion from cardiovascular cell membranes. |
Databáze: | OpenAIRE |
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