RGD Reference Report - Tanshinone IIA prevented brain iron dyshomeostasis in cerebral ischemic rats. - 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 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
Advanced Search (OLGA)

Tanshinone IIA prevented brain iron dyshomeostasis in cerebral ischemic rats.

Authors: Yang, L  Zhang, B  Yin, L  Cai, B  Shan, H  Zhang, L  Lu, Y  Bi, Z 
Citation: Yang L, etal., Cell Physiol Biochem. 2011;27(1):23-30. Epub 2011 Feb 11.
RGD ID: 5688411
Pubmed: PMID:21325818   (View Abstract at PubMed)
DOI: DOI:10.1159/000325202   (Journal Full-text)

BACKGROUND: Tanshinone IIA is a lipid-soluble compound extracted from Chinese herb Danshen which was commonly used in the treatment of cerebrovascular diseases. Brain iron homeostasis is very essential for normal physiological functions of neurons, and brain iron accumulation contributes to many neurological disorders. The present study was aimed to determine whether Tanshinone IIA protects against cerebral ischemic injury via maintaining brain iron homeostasis. METHODS: Wistar Rats were orally administered with Tanshinone IIA (4, 20 and 100 mg/kg/d) for one week, and then subjected to cerebral ischemia by middle cerebral artery occlusion (MCAO) for 2 h. In vitro, cultured neurons were pretreated with Tanshinone IIA (2, 10 and 50 uM) for one week, and then exposed to hypoxia for 24 h. Brain iron content was determined by Flame Atomic Absorption Spectrophotometer and intracellular free iron level was measured by laser scanning Confocal microscopy. Expression levels of iron transport proteins including DMT1, TfR, Fpn1 and Heph were assessed by Western blot technique. RESULTS: Tanshinone IIA pretreatment resulted in a significant reduction of cerebral infarct volume in MCAO rats. Compared with control rats, cerebral ischemia considerably augmented total iron content in the brain of MCAO rats, which was also effectively restricted by Tanshinone IIA pretreatment. MCAO rats exhibited the increased expression of iron influx proteins DMT1 and TfR, and the decreased expression of iron efflux proteins Fpn1 and Heph compared with control rats, which was responsible for elevated iron content in the ischemic brain. Tanshinone IIA pretreatment prevented the dysregulation of these four iron transport proteins and maintained brain iron homeostasis. In vitro studies also confirmed that Tanshinone IIA alleviated the hypoxia-induced decline of cell viability and the overload of intracellular free iron level in neurons through downregulating the expression of DMT1 and TfR, and upregulating the expression of Fpn1 and Heph. CONCLUSION: Tanshinone IIA protected brain tissues against ischemic and hypoxic damage in vivo and in vitro by mediating brain iron homeostasis which was associated with the downregulation of DMT1 and TfR, and the upregulation of Fpn1 and Heph. These results provide new insights into molecular mechanisms of ischemia-induced brain iron abnormalities and suggest maintaining brain iron homeostasis may be a novel therapeutic strategy for ischemic cerebrovascular diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC11A2Humanbrain ischemia  ISOSlc11a2 (Rattus norvegicus)protein:increased expression:brainRGD 
Slc11a2Ratbrain ischemia  IEP protein:increased expression:brainRGD 
Slc11a2Mousebrain ischemia  ISOSlc11a2 (Rattus norvegicus)protein:increased expression:brainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc11a2Ratcellular response to hypoxia  IEP  RGD 
Slc11a2Ratresponse to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc11a2  (solute carrier family 11 member 2)

Genes (Mus musculus)
Slc11a2  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2)

Genes (Homo sapiens)
SLC11A2  (solute carrier family 11 member 2)


Additional Information