Palmitic acid increases apoptosis of neural stem cells via activating c-Jun N-terminal kinase.
Palmitic acid increases apoptosis of neural stem cells via activating c-Jun N-terminal kinase.
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DOI：
10.1016/j.scr.2012.11.008
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发表时间：
2013-03
影响因子：
1.2
通讯作者：
Qiuhuan Yuan;Shidou Zhao;Fu‐wu Wang;Hui Zhang;Zi-jiang Chen;Juntao Wang;Zhen Wang;Zhaoxia Du
中科院分区：
文献类型：
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作者：
Qiuhuan Yuan;Shidou Zhao;Fu‐wu Wang;Hui Zhang;Zi-jiang Chen;Juntao Wang;Zhen Wang;Zhaoxia Du
血浆游离脂肪酸（FFA）水平升高在许多病理条件下是常见的，包括神经系统疾病，其对各种细胞的有害影响已被充分记录。然而，它仍然有待研究是否升高的FFA会对神经干细胞（NSC）的直接影响。在这里，我们报道了棕榈酸（PA）损害细胞活力和增加神经干细胞凋亡显着的剂量和时间依赖性的方式。随着PA处理剂量或时间的增加，在NSC中也观察到Bax和裂解的caspase 3蛋白水平增加，Bcl-2表达降低，而caspase 3表达保持相对不变。与此同时，磷酸-c-Jun N-末端激酶（p-JNK）在PA刺激的NSCs中的表达显著增加;然而，JNK表达似乎稳定。JNK抑制剂能有效抑制PA诱导的NSCs凋亡。磷酸化p38（p-p38）、p38、磷酸化细胞外调节蛋白激酶1/2（p-EKR 1/2）和EKR 1/2的表达不受PA处理的影响。提示血浆FFA水平升高可诱导神经干细胞凋亡，这可能是神经系统疾病认知障碍的潜在机制之一。
Elevated plasma free fatty acid (FFA) level is common in many pathological conditions, including neurological disorders, and their deleterious effects on various cells have been well documented. However, it remains to be investigated whether elevated FFAs would have a direct effect on neural stem cells (NSCs). Here, we reported that palmitic acid (PA) impaired cell viability and increased apoptosis of NSCs significantly in a dose- and time-dependent manner. Increased protein levels of Bax and cleaved caspase 3 coupled with decreased expression of Bcl-2 were also observed in NSCs with increasing dose or time of PA treatment, whereas caspase 3 expression remained relatively unaltered. In parallel to this, the expression of phospho-c-Jun N-terminal kinase (p-JNK) in NSCs challenged with PA was increased significantly; however, JNK expression appeared stable. Remarkably, JNK inhibitor effectively reduced the apoptosis of NSCs induced by PA. The expression of phospho-p38 (p-p38), p38, phospho-extracellular regulated protein kinases 1/2 (p-EKR1/2) and EKR1/2 in NSCs was not affected by PA treatment. In consideration of the above, it is suggested that elevated plasma FFA level may induce apoptosis of NSCs in vivo, and that this might be one of possible underlying mechanisms for the cognitive disturbance in neurological disorders.