TY - JOUR
T1 - Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells
AU - Hsiao, Yung Hsuan
AU - Lin, Ching I.
AU - Liao, Hsiang
AU - Chen, Yue-Hwa
AU - Lin, Shyh-Hsiang
N1 - Publisher Copyright:
© 2014 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2014/11/13
Y1 - 2014/11/13
N2 - Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer’s disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.
AB - Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer’s disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.
KW - Cell cycle arrest
KW - Endoplasmic reticular stress
KW - Neurodegenerative disease
KW - Neurons
KW - Obesity
KW - Palmitic acid
KW - Protein palmitoylation
KW - Saturated fatty acids
UR - http://www.scopus.com/inward/record.url?scp=84910116996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84910116996&partnerID=8YFLogxK
U2 - 10.3390/ijms151120876
DO - 10.3390/ijms151120876
M3 - Article
C2 - 25402647
AN - SCOPUS:84910116996
SN - 1661-6596
VL - 15
SP - 20876
EP - 20899
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 11
ER -