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United States Department of Agriculture

Agricultural Research Service

Title: Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart

Authors
item Razeghi, Peter - UT-HEALTH SCI CENTER
item Baskin, Kedryn - UT-HEALTH SCI CENTER
item Sharma, Saumya - UT-HEALTH SCI CENTER
item Young, Martin
item Stepkowski, Stanislaw - UT-HOUSTON MEDICAL SCHOOL
item Essop, M - HATTER HEART RES INST
item Taegtmeyer, Heinrich - UT-HEALTH SCI CENTER

Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 1, 2006
Publication Date: April 1, 2006
Citation: Razeghi, P., Baskin, K.K., Sharma, S., Young, M.E., Stepkowski, S., Essop, M.F., Taegtmeyer, H. 2006. Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart. Biochemical and Biophysical Research Communications. 342(2):361-364.

Interpretive Summary: The ability of animals to survive relies on continuous beating of the heart. As such, the heart must constantly adapt in response to different situations (for example, exercise or high blood pressure). In order for the heart to adapt, it must replace old proteins with new proteins. This study therefore investigated one potential way in which the heart breaks down old proteins during different stressful situations. We found that the ubiquitin proteasome system was utilized by the heart to increase the removal of old proteins when the heart adapts to multiple disease-inducing conditions (low blood pressure, high blood pressure, low oxygen). These studies have improved our understanding of the early changes that occur in the heart during the development of heart disease.

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

Last Modified: 9/29/2014
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