Bucindolol modulates cardiac remodeling by attenuating oxidative stress in H9c2 cardiac cells exposed to norepinephrine

• Autor(a) principal: Seolin, Bruna Gazzi de Lima
• Data de Publicação: 2019
• Outros Autores: Nemec-Bakk, Ashley, Forsyth, Heidi, Kirk, Stefanie, Araújo, Alex Sander da Rosa, Schenkel, Paulo Cavalheiro, Belló-Klein, Adriane, Khaper, Neelam
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/199535
• topic: Antagonistas adrenérgicos beta; Insuficiência cardíaca; Estresse oxidativo; Norepinefrina

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 β1 and β2 receptors, and has additional α1 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 μM norepinephrine for 24 h in the presence or absence of bucindolol (10 μM) 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-H2DCFDA. 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.