RGD Reference Report - Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling.

Authors: Sun, Y  Tian, Y  Prabha, M  Liu, D  Chen, S  Zhang, R  Liu, X  Tang, C  Tang, X  Jin, H  Du, J 
Citation: Sun Y, etal., Lab Invest. 2010 Jan;90(1):68-82. Epub 2009 Oct 12.
RGD ID: 4145499
Pubmed: PMID:19823174   (View Abstract at PubMed)
DOI: DOI:10.1038/labinvest.2009.102   (Journal Full-text)

Hypoxic pulmonary hypertension is a pathophysiological process important in the development of various cardiopulmonary diseases. Recently, we found that sulfur dioxide could be produced endogenously by pulmonary vessels, and that it showed vascular regulatory capabilities. In this paper, we examined the role of sulfur dioxide in hypoxic pulmonary vascular structural remodeling (HPVSR). A total of 48 Wistar rats were divided into six groups. Rats in the hypoxic group, hypoxic+sulfur dioxide group, and hypoxic+hydroxamate group were left under hypoxic conditions, whereas the control group, control+sulfur dioxide group, and control+hydroxamate group rats were left in room air. For each group, we measured the pulmonary arterial pressure, sulfur dioxide content in plasma and lung tissue, glutamate oxaloacetate transaminase 1 and 2 mRNAs, micro- and ultra-structural changes in pulmonary arteries, proliferation of pulmonary smooth muscle cells, vascular collagen metabolism, pulmonary endothelial cell inflammatory response, and pulmonary vascular endothelin-1 production in the rats. In hypoxic rats, the content of sulfur dioxide in plasma and lung tissue decreased significantly in comparison with those in the control groups, and significant pulmonary hypertension, pulmonary vascular structural remodeling, and increased vascular inflammatory response were also observed in hypoxic rats. Sulfur dioxide donor significantly downregulated Raf-1, mitogen-activated protein kinase kinase-1 (MEK-1) and p-ERK/ERK, and inhibited pulmonary vascular smooth muscle cell proliferation, collagen remodeling and pulmonary vascular endothelial cell nuclear factor-kappaB (NF-kappaB), and intercellular adhesion molecule 1 (ICAM-1) expressions. It also prevented pulmonary hypertension and pulmonary vascular structural remodeling in association with the upregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. Hydroxamate, however, advanced pulmonary hypertension, pulmonary vascular structural remodeling, and inflammatory response of the pulmonary artery in association with a downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. The results suggested that sulfur dioxide markedly inhibited Raf-1, MEK-1, and the phosphorylation of extracellular signal-regulated kinase (ERK), and then inhibited pulmonary arterial smooth muscle cell (PASMC) proliferation induced by hypoxia. The downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway may be involved in the mechanisms responsible for pulmonary hypertension and pulmonary vascular structural remodeling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pulmonary Hypertension, Hypoxia-Induced  ISOGot1 (Rattus norvegicus)4145499; 4145499mRNA:decreased expression:lung (rat)RGD 
Pulmonary Hypertension, Hypoxia-Induced  ISOGot2 (Rattus norvegicus)4145499; 4145499mRNA:decreased expression:lung (rat)RGD 
Pulmonary Hypertension, Hypoxia-Induced  IEP 4145499; 4145499mRNA:decreased expression:lung (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to hypoxia  IEP 4145499 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Got1  (glutamic-oxaloacetic transaminase 1)
Got2  (glutamic-oxaloacetic transaminase 2)
Icam1  (intercellular adhesion molecule 1)

Genes (Mus musculus)
Got1  (glutamic-oxaloacetic transaminase 1, soluble)
Got2  (glutamatic-oxaloacetic transaminase 2, mitochondrial)

Genes (Homo sapiens)
GOT1  (glutamic-oxaloacetic transaminase 1)
GOT2  (glutamic-oxaloacetic transaminase 2)


Additional Information