PDGF suppresses oxidative stress induced Ca2+ overload and calpain activation in neurons.
PDGF suppresses oxidative stress induced Ca2+ overload and calpain activation in neurons.
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DOI：
10.1155/2013/367206
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发表时间：
2013
影响因子：
--
通讯作者：
Sasahara M
中科院分区：
文献类型：
--
作者：
Zheng LS;Ishii Y;Zhao QL;Kondo T;Sasahara M
氧化应激在中风和退行性疾病等神经系统疾病的发病机制中起着关键作用。我们先前已经证明，血小板衍生生长因子(PDGFs)保护神经元免受过氧化氢诱导的氧化应激，并表明PI3K-Akt和MAP激酶是其潜在的机制。钙超载可介导氧化应激和兴奋性毒性的神经毒性效应。我们检测了PDGFs对H_2O_2诱导的原代培养神经元钙超载的影响，以进一步阐明其神经保护机制。H_2O_2以剂量依赖的方式诱导神经元钙超载，而PDGF-BB处理24小时可显著抑制细胞内钙超载。在一项比较研究中，PDGF-BB的抑制作用比PDGF-AA更强。然后，我们评估了钙超载诱导的钙蛋白酶激活，并介导了细胞的凋亡和非凋亡的死亡。H_2O_2以剂量依赖的方式诱导神经元钙蛋白酶的激活。PDGF-BB可完全阻断H_2O_2诱导的钙蛋白酶激活。据我们所知，本研究首次证实了PDGF通过抑制钙超载和钙蛋白酶失活来对抗氧化应激的神经保护作用的机制，并提示PDGF-BB可能是神经疾病的潜在治疗靶点。
Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. We previously demonstrated that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an underlying mechanism. Ca2+ overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs on H2O2-induced Ca2+ overload in primary cultured neurons to further clarify their neuroprotective mechanism. H2O2-induced Ca2+ overload in neurons in a dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. We then evaluated calpain activation, which was induced by Ca2+ overload and mediated both apoptotic and nonapoptotic cell death. H2O2-induced calpain activation in neurons in a dose-dependent manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain activation. To the best of our knowledge, the present study is the first to demonstrate the mechanism underlying the neuroprotective effects of PDGF against oxidative stress via the suppression of Ca2+ overload and inactivation of calpain and suggests that PDGF-BB may be a potential therapeutic target of neurological diseases.
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