Τμήμα Χημείας

Comparative study of interactions of aliskiren and AT1 receptor antagonists with lipid bilayers

Αγγλικά

The renin–angiotensin–aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin is
the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin.
Renin is known to be active both in the circulating blood stream as well as locally, when bound to the (pro)-renin
receptor ((P)RR). In this study we have investigated a possible mechanism of action of aliskiren, in which its accumulation in the plasma membrane is considered as an essential step for effective inhibition. Aliskiren's interactions with model membranes (cholesterol rich and poor) have been investigated by applying different
complementary techniques: differential scanning calorimetry (DSC), Raman spectroscopy, magic angle spinning
(MAS) nuclear magnetic resonance (NMR) spectroscopy and small- and wide-angle X-ray scattering (SAXS and
WAXS). In addition, in silico molecular dynamics (MD) calculations were applied for further confirmation of the
experimental data. Aliskiren's thermal effects on the pre- and main transition of dipalmitoyl-phosphatidylcholine
(DPPC) membranes as well as its topographical position in the bilayer show striking similarities to those of angiotensin II type 1 receptor (AT1R) antagonists. Moreover, at higher cholesterol concentrations aliskiren gets expelled from the membrane just as it has been recently demonstrated for the angiotensin receptor blocker (ARB)
losartan. Thus, we propose that both the AT1R and the (P)RR-bound renin active sites can be efficiently blocked
by membrane-bound ARBs and aliskiren when cholesterol rich membrane rafts/caveolae are formed in the vicinity of the receptor

2015

A.Sadeghpour, M. Rappolt, D. Ntountaniotis, P. Chatzigeorgiou, K. Viras, G. Megariotis, M.Papadopoulos, E. Siapi, G. Mali, T. Mavromoustakos

Biochimica et Biophysica Acta (BBA)

Elsevier

1848

4

984-994

Aliskiren Renin PRR DPPC bilayer

Θετικές Επιστήμες

https://doi.org/http://dx.doi.org/10.1016/j.bbamemed

http://dx.doi.org/10.1016/j.bbamemed

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