Tags

Type your tag names separated by a space and hit enter

Time course of changes in oxidative stress and stress-induced proteins in cardiomyocytes exposed to doxorubicin and prevention by vitamin C.
PLoS One. 2017; 12(7):e0179452.Plos

Abstract

We previously reported that Vitamin C (Vit C) protects against doxorubicin (Dox)-induced cardiotoxicity by reducing oxidative stress, p38 mitogen-activated kinase (MAPK) and p53 activation and rescuing cell death in isolated adult cardiomyocytes. The pattern of activation and the role of oxidative stress as well as down-stream mechanisms for such protection remain elusive. Therefore the present study aims to analyze time-dependant generation of reactive oxygen species (ROS) and the activation of stress induced signalling pathways in cardiomyocytes treated with Dox and Vit C. The data provides further understanding of heart pathophysiology in response to Dox at the cellular level, and may help to optimize the timing of various therapeutic approaches. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to Dox (10 μM), Vit C (25 μM), and Dox + Vit C for different time intervals up to 24 h. p38-JNK (SB203580) and p53 (pifithrin-α) inhibitors were used to determine the role of each respective signalling protein. Dox administration to cardiomyocytes increased the levels of ROS in a time-dependent manner that followed the activation of stress-induced proteins p53, p38 and JNK MAPKs, culminating in an increase in autophagy and apoptosis markers. Dox-induced increase in ROS was alleviated by Vit C adjuvant treatment at all time-points and this was also correlated with blunting of the activation of the studied signaling pathways leading to the prevention of apoptosis and preservation of cell viability. Protective effect of Vit C against the activation of stress induced proteins, autophagy and apoptosis was mainly attributed to its antioxidant properties even though blockage of p38, JNK and p53 by pharmacological inhibitors also suppressed Dox-induced apoptosis. ROS is defined as a key inducer of cardiomyocyte damage under Dox exposure; Vit C could effectively counteract all Dox-induced changes in cardiomyocytes and may potentially be used as an antioxidant adjuvant therapy to protect against Dox-induced cardiomyopathy.

Authors+Show Affiliations

Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28678856

Citation

Ludke, Ana, et al. "Time Course of Changes in Oxidative Stress and Stress-induced Proteins in Cardiomyocytes Exposed to Doxorubicin and Prevention By Vitamin C." PloS One, vol. 12, no. 7, 2017, pp. e0179452.
Ludke A, Akolkar G, Ayyappan P, et al. Time course of changes in oxidative stress and stress-induced proteins in cardiomyocytes exposed to doxorubicin and prevention by vitamin C. PLoS One. 2017;12(7):e0179452.
Ludke, A., Akolkar, G., Ayyappan, P., Sharma, A. K., & Singal, P. K. (2017). Time course of changes in oxidative stress and stress-induced proteins in cardiomyocytes exposed to doxorubicin and prevention by vitamin C. PloS One, 12(7), e0179452. https://doi.org/10.1371/journal.pone.0179452
Ludke A, et al. Time Course of Changes in Oxidative Stress and Stress-induced Proteins in Cardiomyocytes Exposed to Doxorubicin and Prevention By Vitamin C. PLoS One. 2017;12(7):e0179452. PubMed PMID: 28678856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time course of changes in oxidative stress and stress-induced proteins in cardiomyocytes exposed to doxorubicin and prevention by vitamin C. AU - Ludke,Ana, AU - Akolkar,Gauri, AU - Ayyappan,Prathapan, AU - Sharma,Anita K, AU - Singal,Pawan K, Y1 - 2017/07/05/ PY - 2017/01/11/received PY - 2017/05/29/accepted PY - 2017/7/6/entrez PY - 2017/7/6/pubmed PY - 2017/10/7/medline SP - e0179452 EP - e0179452 JF - PloS one JO - PLoS One VL - 12 IS - 7 N2 - We previously reported that Vitamin C (Vit C) protects against doxorubicin (Dox)-induced cardiotoxicity by reducing oxidative stress, p38 mitogen-activated kinase (MAPK) and p53 activation and rescuing cell death in isolated adult cardiomyocytes. The pattern of activation and the role of oxidative stress as well as down-stream mechanisms for such protection remain elusive. Therefore the present study aims to analyze time-dependant generation of reactive oxygen species (ROS) and the activation of stress induced signalling pathways in cardiomyocytes treated with Dox and Vit C. The data provides further understanding of heart pathophysiology in response to Dox at the cellular level, and may help to optimize the timing of various therapeutic approaches. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to Dox (10 μM), Vit C (25 μM), and Dox + Vit C for different time intervals up to 24 h. p38-JNK (SB203580) and p53 (pifithrin-α) inhibitors were used to determine the role of each respective signalling protein. Dox administration to cardiomyocytes increased the levels of ROS in a time-dependent manner that followed the activation of stress-induced proteins p53, p38 and JNK MAPKs, culminating in an increase in autophagy and apoptosis markers. Dox-induced increase in ROS was alleviated by Vit C adjuvant treatment at all time-points and this was also correlated with blunting of the activation of the studied signaling pathways leading to the prevention of apoptosis and preservation of cell viability. Protective effect of Vit C against the activation of stress induced proteins, autophagy and apoptosis was mainly attributed to its antioxidant properties even though blockage of p38, JNK and p53 by pharmacological inhibitors also suppressed Dox-induced apoptosis. ROS is defined as a key inducer of cardiomyocyte damage under Dox exposure; Vit C could effectively counteract all Dox-induced changes in cardiomyocytes and may potentially be used as an antioxidant adjuvant therapy to protect against Dox-induced cardiomyopathy. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28678856/Time_course_of_changes_in_oxidative_stress_and_stress_induced_proteins_in_cardiomyocytes_exposed_to_doxorubicin_and_prevention_by_vitamin_C_ L2 - https://dx.plos.org/10.1371/journal.pone.0179452 DB - PRIME DP - Unbound Medicine ER -