title: Pro-apoptotic effect of anti-β1-adrenergic receptor antibodies in periodontitis patients.
abstract: An anti-β(1)-adrenergic antibody from the sera of periodontitis patients (anti-β(1)-AR IgG) against the second extracellular loop of the human β(1)-adrenoceptor (β(1)-AR) has been shown to cause rat atria apoptosis. The anti-β(1)-AR IgG binds and activates atria β(1)-AR, increasing the intracellular calcium concentration, which, in turn, activates caspases-3, -8, and -9. The β(1)-AR and the post-receptor activation of calcium/calmodulin (CaM) lead to increased inducible nitric oxide synthase (iNOS) activity, with an increase in cyclic GMP (cGMP) accumulation as well as increased JNK phosphorylation and cyclic AMP (cAMP) production. We also observed an apoptotic effect of anti-β(1)-AR IgG, with increased generation of PGE(2). Comparatively, xamoterol, an authentic β(1)-AR agonist, mimicked the autoantibody effect on rat atria β(1)-AR apoptosis. Our results suggest that autoantibodies from the sera of periodontitis patients bind and interact with rat atria β(1)-AR, provoking apoptosis. This implicates a series of modulatory cardiac signaling events that could alter normal heart function and may occur with chronic stimulation of the atria β(1)-AR, which could lead to heart failure. These results suggest an important link between periodontitis and cardiovascular disease.
authors.affiliation: Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Reina
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ganzinelli
authors.forename: Leonor
authors.initials: L
authors.lastname: Sterin-Borda
authors.forename: Enri
authors.initials: E
authors.lastname: Borda
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010518:Periodontitis / Q000628:therapy*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D009712:Nucleotides, Cyclic; D018342:Receptors, Adrenergic, beta-1; D019001:Nitric Oxide Synthase; D048670:MAP Kinase Kinase 4; D020169:Caspases; D015232:Dinoprostone