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Changes in the function of angiotensin II type 1 receptor due to cholesterol depletion from cell membrane

Author:
Matsuo, Yoshino, Suematsu, Yasunori, Idemoto, Yoshiaki, Kuwano, Takashi, Kitajima, Ken, Miura, Shin-ichiro
Source:
Biochemical and biophysical research communications 2019 v.514 no.3 pp. 791-797
ISSN:
0006-291X
Subject:
G-protein coupled receptors, angiotensin II, binding capacity, cardiovascular diseases, cell membranes, cholesterol, cyclic AMP, inositols, phosphates, prognosis
Abstract:
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.
Agid:
6428571