Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells
AbstractHumic 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. View Full-Text
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Li, H.-H.; Lu, F.-J.; Hung, H.-C.; Liu, G.-Y.; Lai, T.-J.; Lin, C.-L. Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells. Int. J. Mol. Sci. 2015, 16, 10426-10442.
Li H-H, Lu F-J, Hung H-C, Liu G-Y, Lai T-J, Lin C-L. Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells. International Journal of Molecular Sciences. 2015; 16(5):10426-10442.Chicago/Turabian Style
Li, Hsin-Hua; Lu, Fung-Jou; Hung, Hui-Chih; Liu, Guang-Yaw; Lai, Te-Jen; Lin, Chih-Li. 2015. "Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells." Int. J. Mol. Sci. 16, no. 5: 10426-10442.