Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart.
BACKGROUND
In skeletal muscle, transcript levels of proteins regulating the ubiquitin proteasome system (UPS) increase with atrophy and decrease with hypertrophy. Whether the same is true for heart muscle is not known.


OBJECTIVE
We set out to characterize the transcriptional profile of regulators of the UPS during atrophy-, hypertrophy-, and hypoxia-induced remodeling of the heart.


RESULTS
Cardiac atrophy was induced by heterotopic transplantation of the rat heart. Left ventricular hypertrophy was induced by banding of the ascending aorta in rats. To study the effects of hypoxemia on the left ventricle, rats were exposed to hypobaric hypoxia. Transcript levels of six known regulators of the UPS, ubiquitin B (UbB), the ubiquitin conjugating enzymes UbcH2 and E2-14kDa, the ubiquitin ligases Mafbx/Atrogin-1 and MuRF-1, and the proteasomal subunit PSMB4 were measured using quantitative RT-PCR. Unloading-induced atrophy increased mRNA levels of UbB and decreased levels of both ubiquitin ligases. Transcript levels of all UPS genes investigated increased in the hypertrophied and hypoxic heart (with the exception of E2-14kDa).


CONCLUSIONS
Cardiac atrophy, hypertrophy, and hypoxemia all increase myocardial UbB expression, suggesting that UbB is a transcriptional marker for load-induced and hypoxia-mediated cardiac remodeling.
Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center, Houston, TX, USA.
Peter
P
Razeghi
Kedryn K
KK
Baskin
Saumya
S
Sharma
Martin E
ME
Young
Stanislaw
S
Stepkowski
M Faadiel
MF
Essop
Heinrich
H
Taegtmeyer
D000818:Animals; D001284:Atrophy; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000473:pathology*; D000860:Hypoxia / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
D014157:Transcription Factors; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex