Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-kappaB activation and expression.
NF-kappaB is a transcription factor implicated in pathological responses that develop during diabetes mellitus, including skeletal muscle atrophy. Given that NF-kappaB activation, protein composition, and content within diabetic skeletal muscle remain generally uncharacterized, a streptozotocin (STZ) model was used to assess NF-kappaB activation, composition, and content. Sprague-Dawley rats were injected with STZ (55 mg/kg) and after 30 days the soleus (SOL), plantaris (PL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were assessed by electrophoresis mobility shift assay and western blotting. NF-kappaB activation was detected in all muscles examined, but was reduced in RG muscles from diabetic animals. Supershifts indicated NF-kappaB was composed primarily of p50 in diabetic and control animals. The content of both p65 and p52 was elevated in SOL and PL muscles, while p52 was decreased in RG. The coactivating protein, Bcl-3, was increased in WG and RG, but decreased in PL. Both p50 and RelB remained unchanged in all tissues examined. All muscles from diabetic animals demonstrated reduced mass when compared to controls, but only the gastrocnemius demonstrated atrophy as reflected by a reduced muscle-to-body mass ratio. In conclusion, diabetic alterations to the contents and activation of the NF-kappaB protein were tissue-specific, but did not appear to alter dimer composition of constitutively bound NF-kappaB. These results indicate that diabetes may alter NF-kappaB activity and expression in a muscle-specific manner.
Frier
Bruce C
BC
School of Kinesiology, Faculty of Health Sciences, Research Institute, University of Western Ontario, London, Ontario, Canada.
Noble
Earl G
EG
Locke
Marius
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
D001786:Blood Glucose; D016328:NF-kappa B; D021122:Protein Subunits