RGD Reference Report - Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase. - Rat Genome Database

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Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase.

Authors: Li, X  Li, H  Lu, N  Feng, Y  Huang, Y  Gao, Z 
Citation: Li X, etal., Biochimie. 2012 Dec;94(12):2620-7. doi: 10.1016/j.biochi.2012.07.019. Epub 2012 Aug 1.
RGD ID: 7488971
Pubmed: PMID:22884880   (View Abstract at PubMed)
DOI: DOI:10.1016/j.biochi.2012.07.019   (Journal Full-text)

Excessive tissue iron levels are associated with the increase of oxidative/nitrative stress which contributes to tissue damage that may elevate the risk of diabetes. Therefore, we investigated the effects of iron on diabetes-associated liver injury and whether iron-related tyrosine nitration participated in this process. Rats were randomly divided into four groups: control, iron overload (300 mg/kg iron dextran, i.p.), diabetic (35 mg/kg of streptozotocin i.p. after administration of a high-fat diet) and diabetic simultaneously treated with iron. Iron supplement markedly increased diabetes-mediated liver damage and hepatic dysfunction by increasing liver/body weight ratio, serum levels of aspartate and alanine aminotransferase, and histological examination, which were correlated with elevated levels of lipid peroxidation, protein carbonyls and tyrosine nitration, oxidative metabolism of nitric oxide, and reduced antioxidant capacity. Consequently, the extent of oxidized/nitrated glucokinase was markedly increased in the iron-treated diabetic rats that contribute to a decrease in its expression and activity. Further studies revealed a significant contribution of iron-induced specific glucokinase nitration sites to its inactivation. In conclusion, iron facilitates diabetes-mediated elevation of oxidative/nitrative stress, simultaneously impairs liver GK, and can be a link between enzymatic changes and hepatic dysfunction. These findings may provide new insight on the role of iron in the pathogenesis of diabetes mellitus.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GCKHumanLiver Injury  ISOGck (Rattus norvegicus)protein:increased nitration more ...RGD 
GckRatLiver Injury  IDA protein:increased nitration more ...RGD 
GckMouseLiver Injury  ISOGck (Rattus norvegicus)protein:increased nitration more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gck  (glucokinase)

Genes (Mus musculus)
Gck  (glucokinase)

Genes (Homo sapiens)
GCK  (glucokinase)


Additional Information