| Autor: |
de Lima-Seolin BG; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90050-170, Brazil.; Medical Sciences Division, Northern Ontario School of Medicine (NOSM), Lakehead University, Thunder Bay, ON P7B 5E1, Canada., Nemec-Bakk A; Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada., Forsyth H; Medical Sciences Division, Northern Ontario School of Medicine (NOSM), Lakehead University, Thunder Bay, ON P7B 5E1, Canada., Kirk S; Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada., da Rosa Araujo AS; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90050-170, Brazil., Schenkel PC; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90050-170, Brazil., Belló-Klein A; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90050-170, Brazil., Khaper N; Medical Sciences Division, Northern Ontario School of Medicine (NOSM), Lakehead University, Thunder Bay, ON P7B 5E1, Canada.; Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada. |
| Abstrakt: |
The increased circulation of norepinephrine, found in the diseased heart as a result of sympathetic nervous system overactivation, is responsible for its cardiotoxic effects including pathological hypertrophy, cell death, and oxidative stress. Bucindolol is a third generation adrenergic blocker, which acts on the β 1 and β 2 receptors, and has additional α 1 antagonist activity. Thus, the aim of this study was to investigate the action of bucindolol on oxidative stress, hypertrophy, cell survival, and cell death signaling pathways in H9c2 cardiac cells exposed to norepinephrine. H9c2 cells were incubated with 10 μ M norepinephrine for 24 h in the presence or absence of bucindolol (10 μ M) treatment for 8 h. Western blot was used to determine the expression of proteins for hypertrophy/survival and death signaling pathways. Flow cytometry was used to assess cell death via caspase-3/7 activity and propidium iodide and reactive oxygen species via measuring the fluorescence of CM-H 2 DCFDA. Norepinephrine exposure resulted in an increase in oxidative stress as well as cell death. This was accompanied by an increased protein expression of LC3B-II/I. The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. In conclusion, bucindolol was able to modulate cardiac remodeling which is mediated by oxidative stress. |
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