Tag Archives: nicotinic acetylcholine receptor
Choline derivatives as natural ligands of mitochondrial nicotinic acetylcholine receptors
O. Lykhmus, M. Izmailov, M. Skok*
Department of Molecular Immunology, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: skok@biochem.kiev.ua
Received: 16 March 2023; Revised: 28 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Nicotinic acetylcholine receptors (nAChRs) regulate mitochondria-driven apoptosis; however, their intracellular ligands are unknown. In the present paper, we show that choline and its derivatives (phosphocholine (PC), L-α-glycerophosphocholine (G-PC) and 1-palmitoyl-sn-glycero-3-phosphocholine (P-GPC)) dose-dependently influence cytochrome c release from isolated mouse liver mitochondria. Choline inhibited Ca2+-stimulated cytochrome c release, while PC attenuated wortmannin-induced cytochrome c release. Small doses of G-PC and P-GPC (up to 0.1 µM) were protective against either Ca2+ or wortmannin, while larger doses (up to 1 µM) stimulated cytochrome c release by themselves. Choline and PC disrupted interaction of VDAC1, Bax and Bcl-2 with mitochondrial α7 nAChRs and favored their interaction with α9 nAChR subunits. It is concluded that choline metabolites can regulate apoptosis by affecting mitochondrial nAChRs.
The effect of amixin and agmatine on cytochrome c release from isolated mitochondria
K. R. Uspenska, G. L. Gergalova, O. Yu. Lykhmus, M. V. Skok
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kate.uspenska@gmail.com
Mitochondrial nicotinic acetylcholine receptors (nAChRs) control permeability transition pore formation and cytochrome c release in the presence of apoptogenic factors. This study demonstrates that pharmacological agents amixin and agmatine affect mitochondrial nAChR functioning: they slightly suppress cytochrome c release from mouse brain and liver mitochondria stimulated with apoptogenic dose of Са2+ and prevent the effect of α7 nAChR agonist PNU282987. We conclude that mitochondria may be one of therapeutic targets of amixin and agmatine.