Puukila Stephanie, Bryan Sean, Laakso Anna, Abdel-Malak Jessica, Gurney Carli, Agostino Adrian, Belló-Klein Adriane, Prasad Kailash, Khaper Neelam
Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
PLoS One. 2015 Mar 30;10(3):e0122852. doi: 10.1371/journal.pone.0122852. eCollection 2015.
Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.
心脏铁过载与心脏功能障碍直接相关，并最终可导致心力衰竭。本研究通过评估H9c2心肌细胞中的氧化应激、炎症和凋亡，检测了亚麻籽成分开环异落叶松脂素二葡萄糖苷（SDG）对铁过载诱导的心脏损伤的影响。细胞用50 μM铁孵育24小时和/或用500 μM SDG预处理24小时。心脏铁过载导致氧化应激增加以及炎症介质肿瘤坏死因子-α、白细胞介素-10和干扰素γ以及基质金属蛋白酶-2和-9的基因表达增加。活性半胱天冬酶3/7活性增加以及叉头框O3a、半胱天冬酶3和Bax的蛋白表达增加，表明凋亡增加。心脏铁过载还导致p70S6激酶1的蛋白表达增加以及AMP激活的蛋白激酶表达减少。SDG预处理消除了铁诱导的氧化应激、炎症和凋亡增加，以及p70S6激酶1增加和AMP激活的蛋白激酶表达减少。在有铁存在的情况下，SDG预处理可防止铁处理导致的超氧化物歧化酶活性降低。基于这些发现，我们得出结论，SDG在铁过载诱导的氧化还原炎症损伤体外模型中具有细胞保护作用，提示SDG在心脏铁过载中具有新的潜在作用。
