An Minae, Kim Minsuk
Department of Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Anat Cell Biol. 2015 Dec;48(4):235-43. doi: 10.5115/acb.2015.48.4.235. Epub 2015 Dec 21.
Kaempferol exerts cardioprotective actions through incompletely understood mechanisms. This study investigated the molecular mechanisms underlying the cardioprotective effects of kaempferol in sinus node dysfunction (SND) heart. Here, we demonstrate that angiotensin II (Ang II) infusion causes SND through oxidized calmodulin kinase II (CaMKII). In contrast to this, kaempferol protects sinus node against Ang II-induced SND. Ang II evoked apoptosis with caspase-3 activation in sinus nodal cells. However, kaempferol lowered the CaMKII oxidization and the sinus nodal cell death. To block the CaMKII oxidization, gene of p47phox, a cytosolic subunit of NADPH oxidase, was deleted using Cas9 KO plasmid. In the absence of p47phox, sinus nodal cells were highly resistance to Ang II-induced apoptosis, suggesting that oxidized-CaMKII contributed to sinus nodal cell death. In Langendorff heart from Ang II infused mice, kaempferol preserved normal impulse formation at right atrium. These data suggested that kaempferol protects sinus node via inhibition of CaMKII oxidization and may be useful for preventing SND in high risk patients.
山奈酚通过尚未完全明确的机制发挥心脏保护作用。本研究调查了山奈酚对窦房结功能障碍（SND）心脏的心脏保护作用的分子机制。在此，我们证明血管紧张素II（Ang II）输注通过氧化钙调蛋白激酶II（CaMKII）导致SND。与此相反，山奈酚可保护窦房结免受Ang II诱导的SND。Ang II在窦房结细胞中通过激活caspase-3引发细胞凋亡。然而，山奈酚降低了CaMKII的氧化和窦房结细胞死亡。为了阻断CaMKII的氧化，使用Cas9敲除质粒删除了NADPH氧化酶的胞质亚基p47phox的基因。在缺乏p47phox的情况下，窦房结细胞对Ang II诱导的细胞凋亡具有高度抗性，表明氧化型CaMKII促成了窦房结细胞死亡。在接受Ang II输注的小鼠的Langendorff心脏中，山奈酚可维持右心房正常的冲动形成。这些数据表明，山奈酚通过抑制CaMKII氧化来保护窦房结，可能对预防高危患者的SND有用。
