title: Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats.
abstract: The aim of this study was to examine the effects of ghrelin on regulation of cardiac inducible nitric oxide synthase (iNOS) activity/expression in high fat (HF), obese rats.For this study, male Wistar rats fed with HF diet (30% fat) for 4 weeks were injected every 24 h for 5 days intracerebroventricularly (ICV) with ghrelin (0.3 nmol/5 µl) or with an equal volume of phosphate buffered saline (PBS). Control rats were ICV injected with an equal volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations were measured in serum, while arginase activity and citrulline concentrations were measured in heart lysate. Protein iNOS and regulatory subunit of nuclear factor-κB (NFκB-p65), phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204) were determined in heart lysate by Western blot. For gene expression of iNOS qRT-PCR was used.Results show significantly (p<0.01) higher serum NO production in ghrelin treated HF rats compared with HF rats. Ghrelin significantly reduced citrulline concentration (p<0.05) and arginase activity (p<0.01) in HF rats. In ghrelin treated HF rats, gene and protein expression of iNOS and NFκB-p65 levels were significantly (p<0.05) increased compared with HF rats. Increased phosphorylation of Akt (p<0.01) and decreased (p<0.05) ERK1/2 phosphorylation were detected in HF ghrelin treated rats compared with HF rats hearts.Results from this study indicate that exogenous ghrelin induces expression and activity of cardiac iNOS via Akt phosphorylation followed by NFκB activation in HF rats.
authors.affiliation: Institute Vinca, Laboratory of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: E
authors.initials: E
authors.lastname: Sudar Milovanovic
authors.affiliation: Institute Vinca, Laboratory of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: A
authors.initials: A
authors.lastname: Jovanovic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Misirkic-Marjanovic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: Lj
authors.initials: Lj
authors.lastname: Vucicevic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: K
authors.initials: K
authors.lastname: Janjetovic
authors.affiliation: Institute Vinca, Laboratory of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: E R
authors.initials: ER
authors.lastname: Isenovic
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D009765:Obesity / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D054439:Ghrelin; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051057:Proto-Oncogene Proteins c-akt