Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells

International Journal of Molecular Sciences

Hsin-Hua Li³  Fung-Jou Lu³  Hui-Chih Hung²  Guang-Yaw Liu¹  Te-Jen Lai³  Chih-Li Lin³ 

[1] Institute of Microbiology & Immunology, Chung Shan Medical University, Taichung 40201, Taiwan; E-Mail:;Department of Life Sciences and Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan; E-Mail:;Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; E-Mails:

关键词: amyloid β;    endoplasmic reticulum stress;    humic acid;    PPARγ coactivator 1α;    sirtuin 1;   

DOI  :  10.3390/ijms160510426

来源: mdpi

【 摘 要 】

Humic acid (HA) is a possible etiological factor associated with for several vascular diseases. It is known that vascular risk factors can directly increase the susceptibility to Alzheimer’s disease (AD), which is a neurodegenerative disorder due to accumulation of amyloid β (Aβ) peptide in the brain. However, the role that HA contributes to Aβ-induced cytotoxicity has not been demonstrated. In the present study, we demonstrate that HA exhibits a synergistic effect enhancing Aβ-induced cytotoxicity in cultured human SK-N-MC neuronal cells. Furthermore, this deterioration was mediated through the activation of endoplasmic reticulum (ER) stress by stimulating PERK and eIF2α phosphorylation. We also observed HA and Aβ-induced cytotoxicity is associated with mitochondrial dysfunction caused by down-regulation of the Sirt1/PGC1α pathway, while in contrast, treating the cells with the ER stress inhibitor Salubrinal, or over-expression of Sirt1 significantly reduced loss of cell viability by HA and Aβ. Our findings suggest a new mechanism by which HA can deteriorate Aβ-induced cytotoxicity through modulation of ER stress, which may provide significant insights into the pathogenesis of AD co-occurring with vascular injury.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.