Depression of proteasome activities during the progression of cardiac dysfunction in pressure-overloaded heart of mice

Tsukamoto, Osamu; Minamino, Tetsuo; Okada, Kenichiro; Shintani, Yasunori; Takashima, Seiji; Kato, Hisakazu; Liao, Yulin; Okazaki, Hiroki; Asai, Mitsutoshi; Hirata, Akio; Fujita, Masashi; Asano, Yoshihiro; Yamazaki, Satoru; Asanuma, Hiroshi; Hori, Masatsugu; Kitakaze, Masafumi

doi:10.1016/j.bbrc.2005.12.120

Cited by 134 publications

(135 citation statements)

References 43 publications

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“…In one study, polyubiquitinated proteins were increased commensurate with decreased UPS activity after thoracic aortic constriction in mice and before the development of heart failure (88). However, in a chronic hypertrophy canine model, proteasome activation was observed in the LV subendocardium (18).…”

Section: Comparing Human Disease With Experimental Model Systemsmentioning

confidence: 99%

“…This has been measured by quantitative Western blot analysis using antibodies that recognize ubiquitin with densitometric analysis of high molecular weight proteins (9,38,71,96,101). Immunolabeling for ubiquitin in fixed tissue sections has also revealed a greater number and size of ubiquitin-positive deposits in failing myocardium compared with controls (25, 29,38,60,88,101). In one study, double labeling for ubiquitin and myosin showed colocalization in large aggregates (38).…”

Section: Ups Function In Human Dcm and Heart Failurementioning

confidence: 99%

“…A functional UPS is critical for normal protein turnover and removes damaged or misfolded proteins in a multistep process (24,39,66,93). Dysfunction of the UPS is rapidly gaining recognition as a potentially important mechanism involved in the pathogenesis of a number of cardiac diseases, including heart failure (38,71,88,93,96,101), cardiomyopathies (12,44,71,78), hypertrophy (18,29,54,72), atrophy (2,72), ischemia-reperfusion (41,67), and atherosclerosis (30), providing a strong rationale for further study of specific mechanisms of proteasome impairment and identification of specific targets for therapy. In vitro and animal models have proven highly valuable in assessing effects of various stressors on the UPS and, in some cases, suggesting a causal link between defective protein clearance and disease phenotypes (14,41,46).…”

Section: Introductionmentioning

confidence: 99%

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The ubiquitin proteasome system in human cardiomyopathies and heart failure

Day

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Comparing Human Disease With Experimental Model Systemsmentioning

confidence: 99%

Section: Ups Function In Human Dcm and Heart Failurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The ubiquitin proteasome system in human cardiomyopathies and heart failure

Day

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…23 The marked accumulation of ubiquitinated proteins in cardiomyocytes of human failing hearts suggests that impairment of the ubiquitin-proteasome system is involved in the development of heart failure. 24,25 Proteasome activities decrease and proapoptotic proteins such as p53 and Bax increase in pressure-overloaded hearts. 25 Meanwhile, it has been reported that Dox enhances the function of the ubiquitin-proteasome system.…”

Section: Circulation Journal Vol72 September 2008mentioning

confidence: 99%

“…24,25 Proteasome activities decrease and proapoptotic proteins such as p53 and Bax increase in pressure-overloaded hearts. 25 Meanwhile, it has been reported that Dox enhances the function of the ubiquitin-proteasome system. 26 Our finding that Dox enhances p300 degradation in cardiac myocytes is compatible with this report.…”

Section: Circulation Journal Vol72 September 2008mentioning

confidence: 99%

Myocardial Regulation of p300 and p53 by Doxorubicin Involves Ubiquitin Pathways

Morimoto

Fujita

Kawamura

et al. 2008

Circ J

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Background Doxorubicin (Dox) depletes p300 from cardiac myocytes and induces apoptosis of these cells. p300 protein possesses ubiquitin ligase activity for the p53 tumor suppressor gene product, catalyzes p53 polyubiqutination, and facilitates p53 degradation in an ubiquitin-dependent manner. The present study investigated the ubiquitin-dependent regulation of p53 by Dox and p300 in cardiac myocytes. Methods and Results Primary cardiac myocytes from neonatal rats were exposed to a proteasome inhibitor, MG132, in culture. MG132 increased both p300 and p53 protein levels in these cells, suggesting that ubiquitindependent degradation is involved in the homeostasis of these proteins. Notably, treatment of cardiac myocytes with Dox decreased the protein levels of p300 but markedly increased those of p53. By immunoprecipitationWestern blotting, it was shown that treatment with Dox decreased poly-ubiquitinated p53 but increased that of p300 in cardiac myocytes. Finally, the overexpression of p300 in cardiomyocytes suppressed the Dox-mediated increase in the p53 level in addition to inhibiting Dox-induced apoptosis. Conclusion Dox reciprocally regulates p300 and p53 through ubiquitin-dependent pathways and that p300, by its ubiquitin ligase activity, is partially involved in the ubiquitin-dependent degradation of p53 in cardiac myocytes. (Circ J 2008; 72: 1506 -1511

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Carboxyl terminus of Hsp70‐interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise

Willis

Min

Wang

et al. 2013

Cell Biochemistry & Function

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The carboxyl terminus of HSP70-interacting protein (CHIP) is a ubiquitin ligase/co-chaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP −/−) suffer decreased survival, enhanced myocardial injury, and increased arrhythmias compared to wild type controls following challenge with cardiac ischemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP −/− mice with voluntary exercise. CHIP −/− mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP −/− mice by serial echocardiography over the five weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signaling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signaling, induced by voluntary running in vivo.

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Depression of proteasome activities during the progression of cardiac dysfunction in pressure-overloaded heart of mice

Cited by 134 publications

References 43 publications

The ubiquitin proteasome system in human cardiomyopathies and heart failure

The ubiquitin proteasome system in human cardiomyopathies and heart failure

Myocardial Regulation of p300 and p53 by Doxorubicin Involves Ubiquitin Pathways

Carboxyl terminus of Hsp70‐interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise

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