Yuan Qiuhuan, Zhao Shidou, Wang Fuwu, Zhang Hui, Chen Zi-Jiang, Wang Juntao, Wang Zhen, Du Zhaoxia, Ling Eng-Ang, Liu Qian, Hao Aijun
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Stem Cell Res. 2013 Mar;10(2):257-66. doi: 10.1016/j.scr.2012.11.008. Epub 2012 Dec 9.
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.
