title: Cigarette smoke adversely affects functions and cell membrane integrity in c-kit+ cardiac stem cells.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, 2100 Gardiner lane, Louisville, KY, 40205, USA, wsumanasekera@sullivan.edu.
authors.forename: Wasana K
authors.initials: WK
authors.lastname: Sumanasekera
authors.forename: David M
authors.initials: DM
authors.lastname: Tran
authors.forename: Thimira U
authors.initials: TU
authors.lastname: Sumanasekera
authors.forename: Nolan
authors.initials: N
authors.lastname: Le
authors.forename: Halle T
authors.initials: HT
authors.lastname: Dao
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Rokosh
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002462:Cell Membrane / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D018384:Oxidative Stress / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D012906:Smoke; D002374:Catalase; D019009:Proto-Oncogene Proteins c-kit; D048049:Extracellular Signal-Regulated MAP Kinases