title: Inflammation decreases the level of alpha7 nicotinic acetylcholine receptors in the brain mitochondria and makes them more susceptible to apoptosis induction.
abstract: α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating inflammatory reactions, as well as the cell viability. They are expressed in both the plasma membrane and mitochondria of eukaryotic cells. Previously we found that neuroinflammation resulted in the decrease of α7 nAChR density in the brain of mice and was accompanied by accumulation of amyloid-beta (Aβ) peptides and memory impairment. In the present paper, it is shown that inflammation induced by either regular bacterial lipopolysaccharide (LPS) injections or immunizations with α7 nAChR extracellular domain (1-208) affected also the brain cell mitochondria. Using various modifications of sandwich ELISA, we observed the decrease of α7 nAChRs and accumulation of Aβ(1-40) and Aβ(1-42) in mitochondria of immunized or LPS-treated mice compared to control ones. Mitochondria of treated mice responded with cytochrome c release to lower Ca(2+) concentrations than mitochondria of control mice and were less sensitive to its attenuation with α7 nAChR agonist PNU282987. It is concluded that inflammation decreases α7 nAChR expression in both mitochondria and cell plasma membrane and makes mitochondria more susceptible to apoptosis induction.
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Olena
authors.initials: O
authors.lastname: Lykhmus
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Galyna
authors.initials: G
authors.lastname: Gergalova
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Zouridakis
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Socrates
authors.initials: S
authors.lastname: Tzartos
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Komisarenko
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine. Electronic address: skok@biochem.kiev.ua.
authors.forename: Maryna
authors.initials: M
authors.lastname: Skok
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001549:Benzamides; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D008070:Lipopolysaccharides; C498513:PNU-282987; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Amyloid β; Apoptosis; Inflammation; Mitochondria; α7 nicotinic acetylcholine receptor; α7-Specific antibodies