RGD Reference Report - Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress. - Rat Genome Database

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Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress.

Authors: Raza, H  Prabu, SK  Robin, MA  Avadhani, NG 
Citation: Raza H, etal., Diabetes. 2004 Jan;53(1):185-94.
RGD ID: 5687773
Pubmed: PMID:14693714   (View Abstract at PubMed)

Oxidative stress is an important factor in the etiology and pathogenesis of diabetes. We investigated changes in mitochondrial production of reactive oxygen species (ROS) and mitochondrial antioxidant defense systems in different tissues of streptozotocin (STZ)-induced diabetic rats. Our results show that increased ROS production and oxidative stress differentially affect mitochondrial and cytosolic glutathione (GSH) metabolism. Of the four tissues investigated, the pancreas, kidney, and brain appear to be affected more severely than the liver. We show a five- to eightfold increase of cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase (GST) A4-4 levels in mitochondria from STZ-treated rat tissues compared with those in nondiabetic rat tissues, suggesting possible roles in the disease process. Transient transfection of COS cells with CYP2E1 cDNA caused a similar accumulation of CYP2E1 and GST A4-4 in mitochondria and increased production of mitochondrial ROS. Our results also show an increase in steady-state levels of Hsp70 in the mitochondrial and cytosolic fractions of different tissues of diabetic rats. These results indicate, for the first time, a marked increase in mitochondrial oxidative stress in target tissues of STZ-treated rats and implicate a direct role for mitochondrial CYP2E1 in the generation of intramitochondrial ROS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOGsta4 (Rattus norvegicus)5687773; 5687773protein:increased expression:pancreas more ...RGD 
Experimental Diabetes Mellitus  IEP 5687773protein:increased expression:pancreas more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsta4  (glutathione S-transferase alpha 4)

Genes (Mus musculus)
Gsta4  (glutathione S-transferase, alpha 4)

Genes (Homo sapiens)
GSTA4  (glutathione S-transferase alpha 4)


Additional Information