<abstract xmlns="http://www.w3.org/1999/xhtml"><p>One of the less known mechanisms of doxorubicin action is the effect on the functioning of the ubiquitin-proteasome degradation system (UPS). So far, the role of impaired proteasome activity in the development of anthracycline cardiomyopathy has not been clarified. It has been shown, however, that doxorubicin decreases the expression of proteins, including the expression of the calcium channel. However, it has not been established whether the observed disturbances are due to the activation of the UPS system by doxorubicin, or due to inhibition of translation or transcription. Therefore, the aim of the study was to evaluate the mRNA and protein expression of plasmalemmal (NaCaX, L-type) and sarcoplasmic reticulum (SERCA2, RyR2) channels in rat embryonic cardiomyocytes treated with doxorubicin and the proteasome inhibitor – bortezomib. The study was conducted utilizing the rat cardiomyocyte H9C2 line that was treated with doxorubicin and bortezomib in different concentrations. After 24 hours incubation, mRNA and protein expression analysis followed. The study did not show any universal mechanism of doxorubicin influence on calcium channel expression. With regard to the Na/Ca exchanger, we saw that DOX decreased the protein level in a proteasome activitydependent manner. Moreover, we noted that the SERCA2 protein expression level was regulated by degradation intensity, however at the same time, no significant effect of doxorubicin on the level of this protein was demonstrated.</p></abstract>

One of the less known mechanisms of doxorubicin action is the effect on the functioning of the ubiquitin-proteasome degradation system (UPS). So far, the role of impaired proteasome activity in the development of anthracycline cardiomyopathy has not been clarified. It has been shown, however, that doxorubicin decreases the expression of proteins, including the expression of the calcium channel. However, it has not been established whether the observed disturbances are due to the activation of the UPS system by doxorubicin, or due to inhibition of translation or transcription. Therefore, the aim of the study was to evaluate the mRNA and protein expression of plasmalemmal (NaCaX, L-type) and sarcoplasmic reticulum (SERCA2, RyR2) channels in rat embryonic cardiomyocytes treated with doxorubicin and the proteasome inhibitor – bortezomib. The study was conducted utilizing the rat cardiomyocyte H9C2 line that was treated with doxorubicin and bortezomib in different concentrations. After 24 hours incubation, mRNA and protein expression analysis followed. The study did not show any universal mechanism of doxorubicin influence on calcium channel expression. With regard to the Na/Ca exchanger, we saw that DOX decreased the protein level in a proteasome activitydependent manner. Moreover, we noted that the SERCA2 protein expression level was regulated by degradation intensity, however at the same time, no significant effect of doxorubicin on the level of this protein was demonstrated.

Evaluation of the impact of the proteasome inhibitor on calcium channel expression in cardiomyocytes treated with doxorubicin

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

One of the less known mechanisms of doxorubicin action is the effect on the functioning of the ubiquitin-proteasome degradation system (UPS). So far, the role...

Evaluation of the impact of the proteasome inhibitor on calcium channel expression in cardiomyocytes treated with doxorubicin

Publié en ligne: 11 avr. 2018

Pages: 18 - 21

Reçu: 25 sept. 2017

Accepté: 13 nov. 2017

DOI: https://doi.org/10.1515/cipms-2018-0004

Mots clés
doxorubicin, bortezomib, proteasome, cardiotoxicity, calcium channels

© 2018 Agnieszka Korga et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Evaluation of the impact of the proteasome inhibitor on calcium channel expression in cardiomyocytes treated with doxorubicin

Publié en ligne: 11 avr. 2018

Pages: 18 - 21

Reçu: 25 sept. 2017

Accepté: 13 nov. 2017

DOI: https://doi.org/10.1515/cipms-2018-0004

Mots clésdoxorubicin, bortezomib, proteasome, cardiotoxicity, calcium channels

© 2018 Agnieszka Korga et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
doxorubicin, bortezomib, proteasome, cardiotoxicity, calcium channels