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.
Oxid Med Cell Longev. 2019 Jul 10;2019:6325424. doi: 10.1155/2019/6325424. eCollection 2019.
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 1 and 2 receptors, and has additional 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 M norepinephrine for 24 h in the presence or absence of bucindolol (10 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-HDCFDA. 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.
去甲肾上腺素的循环增加，由于交感神经系统过度激活，在患病心脏中发现，是其心脏毒性作用的原因，包括病理性肥大、细胞死亡和氧化应激。布新洛尔是第三代肾上腺素能阻滞剂，作用于 1 和 2 受体，并有额外的 1 受体拮抗剂活性。因此，本研究旨在研究布新洛尔在去甲肾上腺素暴露的 H9c2 心肌细胞中的氧化应激、肥大、细胞存活和细胞死亡信号通路中的作用。将 H9c2 细胞用 10 μM 去甲肾上腺素孵育 24 小时，同时用或不用布新洛尔（10 μM）处理 8 小时。Western blot 用于确定肥大/存活和死亡信号通路的蛋白表达。通过 caspase-3/7 活性和碘化丙啶和活性氧的流式细胞术通过测量 CM-HDCFDA 的荧光来评估细胞死亡。去甲肾上腺素暴露导致氧化应激和细胞死亡增加。这伴随着 LC3B-II/I 的蛋白表达增加。参与心脏重塑过程的蛋白激酶 B/雷帕霉素的哺乳动物靶标（Akt/mTOR）通路被去甲肾上腺素激活，并被布新洛尔减轻。总之，布新洛尔能够调节由氧化应激介导的心脏重塑。
