Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: possible role in modulating NADPH oxidase/ROS-mediated NFκB redox signaling cascade.
Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: possible role in modulating NADPH oxidase/ROS-mediated NFκB redox signaling cascade.
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DOI：
10.1038/s41598-017-12060-9
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发表时间：
2017-09-25
影响因子：
4.6
通讯作者：
Padma VV
中科院分区：
文献类型：
--
作者：
Priya LB;Baskaran R;Huang CY;Padma VV
阿霉素(DOX)介导的心肌病是癌症化疗中的一大挑战。黄素酶使阿霉素氧化还原循环，使心脏更容易受到氧化应激的影响，从而导致心功能不全。本研究评估了甲基莲心碱在抑制DOX暴露对H9c2心肌母细胞的分子后果中的作用。甲基莲心碱预处理可增加DOX暴露后的细胞存活率。DOX激活NADPH氧化酶亚基(p22Phox、p47Phox、gp91Phox)为主要事件，随后是[Ca~(2+)]i积累高峰2 h，ROS积累高峰3 h，激活ERK1/2和p38MAPKins，并随时间依赖地激活和移位NFκB，上调COX2和α的表达。甲基莲心碱可调节NADPH氧化酶/ROS系统，抑制MAPKinase和NFκB的激活，减少亚G1期细胞群，同时增加Cyclin D1的表达，从而减少DOX介导的细胞凋亡。这项研究首次证实了DOX毒性背后的分子顺序事件以及甲基莲心碱与H9c2细胞中NADPH氧化酶系统、MAPKines、炎症和凋亡的特定相关性的保护机制。我们的数据表明，甲基莲心碱可作为一种新的药物干预方法，用于预防心血管疾病的继发性并发症。
Doxorubicin (DOX) mediated cardiomyopathy is a major challenge in cancer chemotherapy. Redox-cycling of doxorubicin by flavoenzymes makes the heart more vulnerable to oxidative stress leading to cardiac dysfunction. The present study evaluates the role of neferine, a bisbenzylisoquinoline alkaloid, in curbing the molecular consequences of DOX-exposure in H9c2 cardiomyoblasts. Neferine pre-treatment increased cell viability upon DOX-exposure. DOX activates NADPH oxidase subunits, (p22phox, p47phox, gp91phox) as the primary event followed by peak in [Ca2+]i accumulation by 2 h, ROS by 3 h and activated ERK1/2 and p38 MAPKinases, time dependently along with the activation and translocation of NFκB and up-regulated COX2 and TNF-α expressions. Neferine pre-treatment modulated NADPH oxidase/ROS system, inhibited MAPKinases and NFκB activation, reduced sub G1 cell population and concomitantly increased cyclin D1 expression reducing DOX-mediated apoptosis. The study demonstrates for the first time, the molecular sequential events behind DOX toxicity and the mechanism of protection offered by neferine with specific relevance to NADPH oxidase system, MAPKinases, inflammation and apoptosis in H9c2 cells. Our data suggests the use of neferine as a new approach in pharmacological interventions against cardiovascular disorders as secondary complications.
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影响因子：
7.4
作者：
Dikalov, Sergey
通讯作者：
Dikalov, Sergey
影响因子：
6
作者：
Baskaran, Rathinasamy;Poornima, Paramasivan;Padma, Viswanadha Vijaya
通讯作者：
Padma, Viswanadha Vijaya
莲心碱与莲心碱对人ether-a-go-go相关基因钾通道的影响比较及药理活性分析
影响因子：
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作者：
Dong, Zeng-Xiang;Zhao, Xin;Li, Bao-Xin
通讯作者：
Li, Bao-Xin
影响因子：
10.8
作者：
Liu, Tsun-Jui;Yeh, Yueh-Chiao;Lai, Hui-Chin
通讯作者：
Lai, Hui-Chin
影响因子：
11.4
作者：
Görlach A;Dimova EY;Petry A;Martínez-Ruiz A;Hernansanz-Agustín P;Rolo AP;Palmeira CM;Kietzmann T
通讯作者：
Kietzmann T