Compensatory lung growth in NOS3 knockout mice suggests synthase isoform redundancy
| Autor: | Timothy M. Crombleholme, Stefan Pokall, Lee M. Morris, Foong-Yen Lim, Shuichi Katayama, Charles Klanke, Arturo R. Maldonado, Jose F. Vuletin |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Nitric Oxide Synthase Type III Nitric Oxide Synthase Type II Nitric Oxide Nitric oxide chemistry.chemical_compound Mice Internal medicine medicine Animals cardiovascular diseases RNA Messenger Enzyme Inhibitors Cyclic guanosine monophosphate Cyclic GMP Lung Mice Knockout Messenger RNA Gene knockdown biology business.industry Wild type Endothelial Cells Up-Regulation body regions Nitric oxide synthase Isoenzymes Endocrinology medicine.anatomical_structure NG-Nitroarginine Methyl Ester chemistry Pediatrics Perinatology and Child Health Knockout mouse Models Animal cardiovascular system biology.protein Surgery Female Nitric Oxide Synthase business |
| Zdroj: | European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. 22(2) |
| ISSN: | 1439-359X |
| Popis: | Nitric oxide synthase 3 (NOS3) produces nitric oxide (NO) in endothelial cells, which stimulates cyclic guanosine monophosphate (cGMP) production and thereby mediates pulmonary vasodilation. Inhibition of cGMP enzymatic cleavage by sildenafil might be involved in lung growth stimulating processes in pulmonary hypoplasia. The aim of this study was to discover insights into the transcriptional regulation of NOS3 in a mouse model of compensatory lung growth (CLG). CLG was studied in wild type animals (WT) and NOS3 knockout mice (NOS3-/-) by dry weight, DNA, and protein quantification as well as relative quantification of NOS mRNA. All assessments were done on adult female mice, 10 days after left pneumonectomy (PNX) or sham thoracotomy. Weight ratios of right NOS3-/- lungs were no different than controls. There was a compensatory increase in DNA and a noncompensating increase in protein ratios in NOS3-/- mice compared with controls. Pharmacological knockdown with the pan-NOS inhibitor l-NAME (nitro-arginine methyl ester) reduced CLG by only 8% compared with the d-NAME treated control mice. Relative quantification of lung mRNA revealed no up-regulation of NOS3 expression in WT lungs after PNX, but NOS3-/- lungs showed a 2.6-fold higher inducible NOS2 expression compared with shams. These data suggest that NOS3 loss of function alone does not impair CLG in mice, possibly because of redundancy mechanisms involving NOS2. |
| Databáze: | OpenAIRE |
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