Transcriptional dysregulation of skeletal muscle protein metabolism in streptozotocin-diabetic mice.
The purpose of the study was to evaluate potential changes in expression of genes involved in protein metabolism and myogenic differentiation markers in skeletal muscle of streptozotocin-diabetic mice. Microarray analysis revealed alterations in the expression of 84 gene transcripts in gastrocnemius muscle of diabetic mice. Regarding protein metabolism a marked downregulation in gene transcripts for: general transcription factor IIA1 (-1.88, P=0.016309), TATA box binding protein (-2.17, P=0.037373), eukaryotic translation initiation factor 4E nuclear import factor 1 (-1.61, P=0.037373), eukaryotic translation elongation factor Ibeta2 (-1.95, P=0.010406), ubiquitin-like 5 (-1.67, P=0.024975) and ubiquitin conjugating enzyme 7 interacting protein 1 (-1.68, P=0.016309) was observed. STZ-diabetes caused a drop in the expression of myogenin, whereas myostatin level was significantly elevated. In conclusion, 1) STZ-diabetes attenuates expression of gene transcripts involved in the process of transcription and translation, which may affect skeletal muscle protein synthesis and lead to nitrogen imbalance, 2) impaired expression of gene transcripts involved in the regulation and activity of the ubiquitin-proteasome pathway may contribute to attenuation of mechanisms eliminating damaged proteins in STZ-diabetes, 3) changes in the expression of key myogenic factors, manifested by a decrease in myogenin level and enhancement of myostatin expression may be one of the mechanisms limiting skeletal muscle growth and regeneration associated with diabetes.
Wieteska-Skrzeczynska
W
W
Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland.
Grzelkowska-Kowalczyk
K
K
Jank
M
M
Maciejewski
H
H
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
D000943:Antigens, Differentiation; D009124:Muscle Proteins