MG132 treatment attenuates cardiac remodeling and dysfunction following aortic banding in rats via the NF-κB/TGFβ1 pathway

Ma, Yuedong; Chen, Baolin; Liú, Dan; Yang, Yang; Xiong, Zhaojun; Zeng, Junyi; Dong, Yugang

doi:10.1016/j.bcp.2011.03.009

Cited by 41 publications

(32 citation statements)

References 34 publications

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“…Authors more often indicate a possible systemic toxic effect and even an increase in the mortality risk in the reports where there were late effects of MG-132 and the effects of multiple doses of the MG-132 studied [29,37]. A dose of 10 mg/kg of body weight (cumulative dose of above 30 mg/kg) provided intraperitoneally seems to lead to high mortality, although rats can survive a cumulative dose of 105 mg/kg [7] delivered in 14 doses during seven days subcutaneously.…”

Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

“…It has been reported that [19] in experimental inflammatory bo wel disease MG-132 in vivo reduced T cell-mediated intestinal inflammation but significantly suppressed cell migration and epithelial cell proliferation. MG-132 also has an influence on the cardiovascular system [8,29,34]. In a low dose (0.1 mg/kg) MG-132 administered intraperitoneally once per day even for 2 or 8 weeks may effectively prevent cardiac remodelling and dysfunction in pressure-overloaded hearts without marked drug toxicity [29].…”

Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

“…MG-132 also has an influence on the cardiovascular system [8,29,34]. In a low dose (0.1 mg/kg) MG-132 administered intraperitoneally once per day even for 2 or 8 weeks may effectively prevent cardiac remodelling and dysfunction in pressure-overloaded hearts without marked drug toxicity [29]. The effects of intraperitoneal injection of MG-132 was also studied on urinary [37], musculoskeletal [20,42], and respiratory systems [28].…”

Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

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Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Wójcik

Spodnik²,

Spodnik³

et al. 2014

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Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

Section: Systemic Administration Of Proteasome Inhibitionmentioning

confidence: 99%

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Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Wójcik

Spodnik²,

Spodnik³

et al. 2014

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“…However, studies have been contradictory, showing either increased or decreased proteasomal enzyme activity in the afterload stressed LV (31, 43). Other models have demonstrated both cardioprotective (9, 21, 25, 59) and cardiotoxic (12,20,27,32,45,46) roles of the UPS via regulation of apoptosis, NF-B signaling, and oxidative stress.Although much is known about the molecular mechanisms of LVH and LV failure (LVF), the mechanisms underlying right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) are less understood. RVH and RVF are a major cause of morbidity and mortality in patients with pulmonary hypertension and represent long-term risks for patients with surgically corrected congenital heart diseases such as tetralogy of Fallot, L-transposition of the great arteries, and hypoplastic left heart (4, 34).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure

Rajagopalan

Zhao

Reddy

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Alterations in the ubiquitin-proteasome system (UPS) have been described in left ventricular hypertrophy and failure, although results have been inconsistent. The role of the UPS in right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) is unknown. Given the greater percent increase in RV mass associated with RV afterload stress, as present in many congenital heart lesions, we hypothesized that alterations in the UPS could play an important role in RVH/RVF. UPS expression and activity were measured in the RV from mice with RVH/RVF secondary to pulmonary artery constriction (PAC). Epoxomicin and MG132 were used to inhibit the proteasome, and overexpression of the 11S PA28␣ subunit was used to activate the proteasome. PAC mice developed RVH (109.3% increase in RV weight to body weight), RV dilation with septal shift, RV dysfunction, and clinical RVF. Proteasomal function (26S ␤5 chymotrypsin-like activity) was decreased 26% (P Ͻ 0.05). Protein expression of 19S subunit Rpt5 (P Ͻ 0.05), UCHL1 deubiquitinase (P Ͻ 0.0001), and Smurf1 E3 ubiquitin ligase (P Ͻ 0.01) were increased, as were polyubiquitinated proteins (P Ͻ 0.05) and free-ubiquitins (P ϭ 0.05). Pro-apoptotic Bax was increased (P Ͻ 0.0001), whereas anti-apoptotic Bcl-2 decreased (P Ͻ 0.05), resulting in a sixfold increase in the Bax/Bcl-2 ratio. Proteasomal inhibition did not accelerate RVF. However, proteasome enhancement by cardiacspecific proteasome overexpression partially improved survival. Proteasome activity is decreased in RVH/RVF, associated with upregulation of key UPS regulators and pro-apoptotic signaling. Enhancement of proteasome function partially attenuates RVF, suggesting that UPS dysfunction contributes to RVF. ubiquitin; proteasome; right ventricle; cardiac hypertrophy; heart failure PATHOLOGIC HYPERTROPHY IS an important adaptation to stressors varying from ischemia to hypertension as well as many forms of congenital heart disease. Chronic hypertrophy-inducing stress can lead to fibrosis, decreased contractile function, and ultimately heart failure. Pressure overload hypertrophy is associated with a marked increase in protein synthesis at a rate exceeding degradation (57), the most dramatic the heart experiences since early development. Under normal circumstances, the proteins of the heart turn over at a rate that would replace all in 30 days (15,33,50). More than 70% of protein turnover is regulated by the ubiquitin-proteasome system (UPS) (18,56,74), involving signaling the target by covalent attachment of ubiquitin and degradation of tagged proteins by the 26S proteasome complex with release of ubiquitins by deubiquitinating enzymes. Three peptidase activities, chymotrypsin-like, trypsin-like, and caspase-like activities, have been assigned to the ␤ 5 , ␤ 2 , and ␤ 1 subunits, respectively, of the 20S core proteasomal complex, capped by 19S regulatory and/or 11S activator complexes. The UPS also interacts with lysosomal (autophagy dependent or independent) and other protease-specific pathways within the cardiomyocyte (17, 71)....

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Protein turnover in the failing heart: an ever‐changing landscape

Cheema

Sabbah

Greene

et al. 2017

European J of Heart Fail

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MG132 treatment attenuates cardiac remodeling and dysfunction following aortic banding in rats via the NF-κB/TGFβ1 pathway

Cited by 41 publications

References 34 publications

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure

Protein turnover in the failing heart: an ever‐changing landscape

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