TY - JOUR
T1 - Cigarette smoke adversely affects functions and cell membrane integrity in c-kit+ cardiac stem cells
AU - Sumanasekera, Wasana K.
AU - Tran, David M.
AU - Sumanasekera, Thimira U.
AU - Le, Nolan
AU - Dao, Halle T.
AU - Rokosh, Gregg D.
N1 - Funding Information:
Acknowledgements We acknowledge Sullivan University System for providing funding to conduct this research. We are thankful to Dr. H. Tran, Founding Dean of Sullivan University College of Pharmacy, Dr. Y. Pathak, former Pharmaceutical Sciences Department Chair and Pharmaceutical Sciences Department faculty for their support, encouragement, and help with the establishment of research facilities. We would also like to acknowledge Dr. Piero Anversa, Brigham and Women’s hospital, Boston, MA and Dr. Roberto Bolli, University of Louisville for providing c-kit positive rat cardiac stem cell line. Special thanks go to Sullivan University College of Pharmacy rotation students and student volunteers for assisting with some experiments.
PY - 2014/4
Y1 - 2014/4
N2 - Cigarette smoking is a major risk factor for numerous diseases including cardiovascular diseases. Exposure to cigarette smoke (CS) leads to increased cardiovascular risk, myocardial injury, and mortality. Stem cell therapy is one of the promising therapeutic options available to treat myocardial injuries. Understanding the impact of cigarette smoke extract (CSE) on stem cell function would be valuable in determining the risk passed on during transplant. In this study, the impact of CSE on cardiac stem cell (CSC) functions was investigated using c-kit+ rat cardiac stem cells as the experimental model. Here, we hypothesized that CSE attenuates CSC membrane integrity, causes cytotoxicity, and affects many CSC functions via multiple mechanisms including modulation of extracellular stress-regulated kinase (ERK) (44/42) signaling and oxidative stress. The effects of CSE on CSCs were examined in vitro. Based on a published method, CSE was prepared. CSE-induced ERK signaling was detected by western blotting. CSE-induced modulation of catalase activity was also measured. Functional modulations due to CSE were examined via several methods including Apostain, BrdU, and LDH assays. In agreement with the CSE-induced activation of ERK, CSE-induced reduction in viability, migration, and increase in both cytotoxicity and para-cellular permeability were observed in CSCs. These results suggest that CSE impaired CSC responses that contribute to decreased ability of CSC to respond to stress or injury leading to exacerbation of the damage. Our findings will contribute to the understanding of the discipline and might contribute to the development of stem cell therapy approaches in the future.
AB - Cigarette smoking is a major risk factor for numerous diseases including cardiovascular diseases. Exposure to cigarette smoke (CS) leads to increased cardiovascular risk, myocardial injury, and mortality. Stem cell therapy is one of the promising therapeutic options available to treat myocardial injuries. Understanding the impact of cigarette smoke extract (CSE) on stem cell function would be valuable in determining the risk passed on during transplant. In this study, the impact of CSE on cardiac stem cell (CSC) functions was investigated using c-kit+ rat cardiac stem cells as the experimental model. Here, we hypothesized that CSE attenuates CSC membrane integrity, causes cytotoxicity, and affects many CSC functions via multiple mechanisms including modulation of extracellular stress-regulated kinase (ERK) (44/42) signaling and oxidative stress. The effects of CSE on CSCs were examined in vitro. Based on a published method, CSE was prepared. CSE-induced ERK signaling was detected by western blotting. CSE-induced modulation of catalase activity was also measured. Functional modulations due to CSE were examined via several methods including Apostain, BrdU, and LDH assays. In agreement with the CSE-induced activation of ERK, CSE-induced reduction in viability, migration, and increase in both cytotoxicity and para-cellular permeability were observed in CSCs. These results suggest that CSE impaired CSC responses that contribute to decreased ability of CSC to respond to stress or injury leading to exacerbation of the damage. Our findings will contribute to the understanding of the discipline and might contribute to the development of stem cell therapy approaches in the future.
KW - Apoptosis
KW - Cardiovascular
KW - Cigarette smoke
KW - Cytotoxicity
KW - ERK
KW - Stem cell therapy
UR - http://www.scopus.com/inward/record.url?scp=84897529809&partnerID=8YFLogxK
U2 - 10.1007/s10565-014-9273-6
DO - 10.1007/s10565-014-9273-6
M3 - Article
C2 - 24633465
AN - SCOPUS:84897529809
SN - 0742-2091
VL - 30
SP - 113
EP - 125
JO - Cell Biology and Toxicology
JF - Cell Biology and Toxicology
IS - 2
ER -