title: Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy.
abstract: Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α1-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy.
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto Interuniversitario di Miologia, Istituto di Neuroscienze del CNR, Padova, Italy.
authors.forename: Carmelina
authors.initials: C
authors.lastname: Chiarello
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto Interuniversitario di Miologia, Istituto di Neuroscienze del CNR, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bortoloso
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto Interuniversitario di Miologia, Istituto di Neuroscienze del CNR, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carpi
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto Interuniversitario di Miologia, Istituto di Neuroscienze del CNR, Padova, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Furlan
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto Interuniversitario di Miologia, Istituto di Neuroscienze del CNR, Padova, Italy. Electronic address: pompeo.volpe@unipd.it.
authors.forename: Pompeo
authors.initials: P
authors.lastname: Volpe
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D000072233:Homer Scaffolding Proteins; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009320:Atrial Natriuretic Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D009638:Norepinephrine