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Akude 2011 Diabetes
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Diabetes  +
Has abstract '''OBJECTIVE:''' Impairments in mitochondr
'''OBJECTIVE:''' Impairments in mitochondrial function have been proposed to play a role in the etiology of diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in axons of sensory neurons in type 1 diabetes is due to abnormal activity of the respiratory chain and an altered mitochondrial proteome. '''RESEARCH DESIGN AND METHODS:''' Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in mitochondria from dorsal root ganglia (DRG) of control, 22-week-old streptozotocin (STZ)-diabetic rats, and diabetic rats treated with insulin. Rates of oxygen consumption and complex activities in mitochondria from DRG were measured. Fluorescence imaging of axons of cultured sensory neurons determined the effect of diabetes on mitochondrial polarization status, oxidative stress, and mitochondrial matrix-specific reactive oxygen species (ROS). '''RESULTS:''' Proteins associated with mitochondrial dysfunction, oxidative phosphorylation, ubiquinone biosynthesis, and the citric acid cycle were downregulated in diabetic samples. For example, cytochrome c oxidase subunit IV (COX IV; a Complex IV protein) and NADH dehydrogenase Fe-S protein 3 (NDUFS3; a Complex I protein) were reduced by 29 and 36% (''P'' < 0.05), respectively, in diabetes and confirmed previous Western blot studies. Respiration and mitochondrial complex activity was significantly decreased by 15 to 32% compared with control. The axons of diabetic neurons exhibited oxidative stress and depolarized mitochondria, an aberrant adaption to oligomycin-induced mitochondrial membrane hyperpolarization, but reduced levels of intramitochondrial superoxide compared with control. '''CONCLUSIONS:''' Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the [[respiratory chain]] was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.
neurons under high glucose concentration.  +
Has info [ PMID: 20876714 Open Access]  +
Has publicationkeywords Dorsal root ganglion (DRG)  +
Has title Akude E, Zherebitskaya E, Chowdhury SK, Sm
Akude E, Zherebitskaya E, Chowdhury SK, Smith DR, Dobrowsky RT, Fernyhough P (2011) Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats. Diabetes 60:288-97.
ns from diabetic rats. Diabetes 60:288-97.  +
Instrument and method Oxygraph-2k  +
Mammal and model Rat  +
MiP area Respiration  +
Pathways N  + , CIV  +
Preparation Isolated mitochondria  +
Tissue and cell Nervous system  +
Was published by MiPNetLab CA Winnipeg Fernyhough P +
Was published in journal Diabetes +
Was published in year 2011  +
Was written by Akude E + , Zherebitskaya E + , Roy Chowdhury SK + , Smith DR + , Dobrowsky RT + , Fernyhough P +
Categories Publications
Modification date
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17:10:43, 1 April 2018  +
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