YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCδ/Drp1-Mediated Excessive Mitochondrial Fission.

Yingqiong Xu,Zhen Gao,Jiangwei Zhang,Xinyi Ye,Junping Kou,Boyang Yu,Yazheng Zhao,Yan Wang,Guangyun Wang,Guosheng Cao,Yuanyuan Zhang

doi:10.1155/2017/1832093

Yingqiong Xu, Zhen Gao + Show 9 more

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https://doi.org/10.1155/2017/1832093

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Abstract

YiQiFuMai (YQFM) powder injection has been reported to be used in cardiovascular and nervous system diseases with marked efficacy. However, as a treatment against diseases characterized by hypoxia, lassitude, and asthenia, the effects and underlying mechanisms of YQFM in neuronal mitochondrial function and dynamics have not been fully elucidated. Here, we demonstrated that YQFM inhibited mitochondrial apoptosis and activation of dynamin-related protein 1 (Drp1) in cerebral ischemia-injured rats, producing a significant improvement in cerebral infarction and neurological score. YQFM also attenuated oxidative stress-induced mitochondrial dysfunction and apoptosis through increasing ATP level and mitochondria membrane potential (Δψm), inhibiting ROS production, and regulating Bcl-2 family protein levels in primary cultured neurons. Moreover, YQFM inhibited excessive mitochondrial fission, Drp1 phosphorylation, and translocation from cytoplasm to mitochondria induced by oxidative stress. We provided the first evidence that YQFM inhibited the activation, association, and translocation of PKCδ and Drp1 upon oxidative stress. Taken together, we demonstrate that YQFM ameliorates ischemic stroke-induced neuronal apoptosis through inhibiting mitochondrial dysfunction and PKCδ/Drp1-mediated excessive mitochondrial fission. These findings not only put new insights into the unique neuroprotective properties of YQFM associated with the regulation of mitochondrial function but also expand our understanding of the underlying mechanisms of ischemic stroke.

Highlights

Ischemic stroke is a devastating cerebral vascular disease induced by insufficient cerebral blood flow, which is characterized by high mortality and morbidity [1]
YQFM pretreatment inhibited the interaction and translocation of dynamin-related protein 1 (Drp1) and PKCδ from cytoplasm to mitochondria, the effects of which were paralleled with rottlerin and Mdivi-1. These results demonstrated that the mechanism of YQFM on mitochondrial fission is mediated through the association and translocation of PKCδ and Drp1 in oxidative stress-induced neuronal apoptosis
We explored the novel mechanisms of YQFM against neuronal injury through inhibiting PKCδ/

Summary

Introduction

Ischemic stroke is a devastating cerebral vascular disease induced by insufficient cerebral blood flow, which is characterized by high mortality and morbidity [1]. The production of reactive oxygen species (ROS) is immediately increased after acute ischemic stroke and rapidly overwhelms antioxidants [3]. Oxidative stress-induced neuronal apoptosis and mitochondrial dysfunction are critical to the development of ischemic stroke [4]. Exogenous H2O2 has been reported to induce neuronal cell apoptosis in the central nervous system (CNS) and has been used to produce oxidative stress-induced apoptosis models [6]. It has been used in a model of cerebral ischemic in vitro [7, 8]

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