Changes in composition and activities of 26S proteasomes under the action of doxorubicin—apoptosis inductor of erythroleukemic K562 cells

Цимоха, А. С.; Mittenberg, A. G.; Куличкова, В. А.; Kozhukharova, Irina; Gause, L. N.; Konstantinova, Irina D.

doi:10.1016/j.cellbi.2007.01.018

Cited by 21 publications

(13 citation statements)

References 67 publications

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“…NFAT5 has been reported to play a role in cardiomyocyte survival [49,50]. Previously, Dox induced apoptosis have been suggested to result from proteasome-mediated degradation of NFAT5 [44–51]. In the current study, we found a significant increase in NFAT3 and a decrease in NFAT5 levels in myocardial tissue from Dox treated animals.…”

Section: Discussionsupporting

confidence: 71%

Prophylactic supplementation of resveratrol is more effective than its therapeutic use against doxorubicin induced cardiotoxicity

et al. 2017

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Resveratrol (RSV), a polyphenolic compound and naturally occurring phytoalexin, has been reported to exert cardio-protective effects in several animal studies. However, the outcome of initial clinical trials with RSV was less effective compared to pre-clinical studies. Therefore, RSV treatment protocols need to be optimized. In this study we evaluated prophylactic versus therapeutic effect of resveratrol (RSV) in mitigating doxorubicin (Dox)-induced cardiac toxicity in rats. To investigate prophylactic effects, RSV was supplemented for 2 weeks along with Dox administration. After 2 weeks, Dox treatment was stopped and RSV was continued for another 4 weeks. To study therapeutic effects, RSV treatment was initiated after 2 weeks of Dox administration and continued for 4 weeks. Both prophylactic and therapeutic use of RSV mitigated Dox induced deterioration of cardiac function as assessed by echocardiography. Also RSV treatment (prophylactic and therapeutic) prevented Dox induced myocardial damage as measured by cardiac enzymes (LDH and CK-MB) in serum. Which was associated with decrease in Dox induced myocardial apoptosis and fibrosis. Interestingly our study also reveals that prophylactic use of RSV was more effective than its therapeutic use in mitigating Dox induced apoptosis and fibrosis in the myocardium. Therefore, prophylactic use of resveratrol may be projected as a possible future adjuvant therapy to minimize cardiotoxic side effects of doxorubicin in cancer patients.

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Section: Discussionsupporting

confidence: 71%

Prophylactic supplementation of resveratrol is more effective than its therapeutic use against doxorubicin induced cardiotoxicity

et al. 2017

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“…Dox has been shown to both inhibit and activate UPS proteolytic activities in experimental settings (10,24,45). The present study reveals that a critical factor for this dichotomy is likely the dosage of Dox.…”

Section: Discussionmentioning

confidence: 71%

“…Dox and its metabolites induced posttranslational modifications to UPS substrates, and proteasome subunits may also play a role in its effects on UPS-mediated protein degradation. Tsimokha et al (45) recently reported that Dox treatment can increase the phosphorylation of proteasome subunits and enhance the chymotrypsinlike activity of the 26S proteasome in cultured neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome

Liu

Zheng²,

Tang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The ubiquitin proteasome system (UPS) degrades abnormal proteins and most unneeded normal proteins, thereby playing a critical role in protein homeostasis in the cell. Proteasome inhibition is effective in treating certain forms of cancer, while UPS dysfunction is increasingly implicated in the pathogenesis of many severe and yet common diseases. It has been previously shown that doxorubicin (Dox) enhances the degradation of a UPS surrogate substrate in mouse hearts. To address the underlying mechanism, in the present study, we report that 1) Dox not only enhances the degradation of an exogenous UPS reporter (GFPu) but also antagonizes the proteasome inhibitor-induced accumulation of endogenous substrates (e.g., beta-catenin and c-Jun) of the UPS in cultured NIH 3T3 cells and cardiomyocytes; 2) Dox facilitates the in vitro degradation of GFPu and c-Jun by the reconstituted UPS via the enhancement of proteasomal function; 3) Dox at a therapeutically relevant dose directly stimulates the peptidase activities of purified 20S proteasomes; and 4) Dox increases, whereas proteasome inhibition decreases, E3 ligase COOH-terminus of heat shock protein cognate 70 in 3T3 cells via a posttranscriptional mechanism. These new findings suggest that Dox activates the UPS by acting directly on both the ubiquitination apparatus and proteasome.

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“…Proteasomes were extracted and purified from cytosol using a multistep purification procedure as described previously [56]. …”

Section: Methodsmentioning

confidence: 99%

DNA damage modulates interactions between microRNAs and the 26S proteasome

et al. 2014

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26S proteasomes are known as major non-lysosomal cellular machines for coordinated and specific destruction of ubiquitinylated proteins. The proteolytic activities of proteasomes are controlled by various post-translational modifications in response to environmental cues, including DNA damage. Besides proteolysis, proteasomes also associate with RNA hydrolysis and splicing. Here, we extend the functional diversity of proteasomes by showing that they also dynamically associate with microRNAs (miRNAs) both in the nucleus and cytoplasm of cells. Moreover, DNA damage induced by an anti-cancer drug, doxorubicin, alters the repertoire of proteasome-associated miRNAs, enriching the population of miRNAs that target cell cycle checkpoint regulators and DNA repair proteins. Collectively, these data uncover yet another potential mode of action for proteasomes in the cell via their dynamic association with microRNAs.

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Changes in composition and activities of 26S proteasomes under the action of doxorubicin—apoptosis inductor of erythroleukemic K562 cells

Cited by 21 publications

References 67 publications

Prophylactic supplementation of resveratrol is more effective than its therapeutic use against doxorubicin induced cardiotoxicity

Prophylactic supplementation of resveratrol is more effective than its therapeutic use against doxorubicin induced cardiotoxicity

A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome

DNA damage modulates interactions between microRNAs and the 26S proteasome

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