Abstract
Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and NF-κB was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not NF-κB, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, NF-κB expression levels were not related to UPS function.
| Original language | English |
|---|---|
| Pages (from-to) | 144-152 |
| Number of pages | 9 |
| Journal | Korean Journal of Thoracic and Cardiovascular Surgery |
| Volume | 50 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
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Keywords
- Androgen
- Cardiomyopathy
- Hypertrophic
- MG132
- NF-kappa B
- Proteasome inhibitors
- Receptors
- Ubiquitins
ASJC Scopus subject areas
- Surgery
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine
Cite this
Effects of a proteasome inhibitor on cardiomyocytes in a pressure-overload hypertrophy rat model : An animal study. / Kim, In Sub; Jo, Won-Min.
In: Korean Journal of Thoracic and Cardiovascular Surgery, Vol. 50, No. 3, 01.01.2017, p. 144-152.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of a proteasome inhibitor on cardiomyocytes in a pressure-overload hypertrophy rat model
T2 - An animal study
AU - Kim, In Sub
AU - Jo, Won-Min
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and NF-κB was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not NF-κB, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, NF-κB expression levels were not related to UPS function.
AB - Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and NF-κB was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not NF-κB, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, NF-κB expression levels were not related to UPS function.
KW - Androgen
KW - Cardiomyopathy
KW - Hypertrophic
KW - MG132
KW - NF-kappa B
KW - Proteasome inhibitors
KW - Receptors
KW - Ubiquitins
UR - http://www.scopus.com/inward/record.url?scp=85020057053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020057053&partnerID=8YFLogxK
U2 - 10.5090/kjtcs.2017.50.3.144
DO - 10.5090/kjtcs.2017.50.3.144
M3 - Article
VL - 50
SP - 144
EP - 152
JO - Cancer Research and Treatment
JF - Cancer Research and Treatment
SN - 1598-2998
IS - 3
ER -