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Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.

Hsiao YH, Lin CI, Liao H, Chen YH, Lin SH - Int J Mol Sci (2014)

Bottom Line: We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells.Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease.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.

View Article: PubMed Central - PubMed

Affiliation: Department of School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. m507100009@tmu.edu.tw.

ABSTRACT
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.

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Relative fatty acid contents of SH-SY5Y cells treated with palmitic acid (PA) or oleic acid (OA) at 0, 3, 6, 10, 20 and 24 h. The fatty acid composition was analyzed by gas chromatography after 0~24 h of incubation with (A) 0.3 mM PA and (B) 0.3 mM OA. Data were analyzed by a one-way analysis of variance (ANOVA), followed by the LSD test, and are presented as the mean ± SD. * p < 0.05, ** p < 0.01 vs. the control group (n = 3).
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ijms-15-20876-f001: Relative fatty acid contents of SH-SY5Y cells treated with palmitic acid (PA) or oleic acid (OA) at 0, 3, 6, 10, 20 and 24 h. The fatty acid composition was analyzed by gas chromatography after 0~24 h of incubation with (A) 0.3 mM PA and (B) 0.3 mM OA. Data were analyzed by a one-way analysis of variance (ANOVA), followed by the LSD test, and are presented as the mean ± SD. * p < 0.05, ** p < 0.01 vs. the control group (n = 3).

Mentions: FA uptake was analyzed by gas chromatography. As shown in Figure 1A, the PA content significantly increased in cells compared to the control group after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM PA (p < 0.05). The PA content increased by 69% ± 12%, 138% ± 27%, 185% ± 34%, 246% ± 45% and 346% ± 67%, respectively, in SH-SY5Y after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM PA (Figure 1A). On the other hand, the OA content also increased by 57% ± 12%, 243% ± 27%, 300% ± 34%, 400% ± 45% and 471% ± 67%, respectively, after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM OA (Figure 1B). These data suggested that FA uptake was elevated by FA treatment in SH-SY5Y cells. The treated FAs, including PA and OA, were incorporated into SH-SY5Y cells from the medium and reached significant levels after 3 h of incubation.


Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.

Hsiao YH, Lin CI, Liao H, Chen YH, Lin SH - Int J Mol Sci (2014)

Relative fatty acid contents of SH-SY5Y cells treated with palmitic acid (PA) or oleic acid (OA) at 0, 3, 6, 10, 20 and 24 h. The fatty acid composition was analyzed by gas chromatography after 0~24 h of incubation with (A) 0.3 mM PA and (B) 0.3 mM OA. Data were analyzed by a one-way analysis of variance (ANOVA), followed by the LSD test, and are presented as the mean ± SD. * p < 0.05, ** p < 0.01 vs. the control group (n = 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264201&req=5

ijms-15-20876-f001: Relative fatty acid contents of SH-SY5Y cells treated with palmitic acid (PA) or oleic acid (OA) at 0, 3, 6, 10, 20 and 24 h. The fatty acid composition was analyzed by gas chromatography after 0~24 h of incubation with (A) 0.3 mM PA and (B) 0.3 mM OA. Data were analyzed by a one-way analysis of variance (ANOVA), followed by the LSD test, and are presented as the mean ± SD. * p < 0.05, ** p < 0.01 vs. the control group (n = 3).
Mentions: FA uptake was analyzed by gas chromatography. As shown in Figure 1A, the PA content significantly increased in cells compared to the control group after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM PA (p < 0.05). The PA content increased by 69% ± 12%, 138% ± 27%, 185% ± 34%, 246% ± 45% and 346% ± 67%, respectively, in SH-SY5Y after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM PA (Figure 1A). On the other hand, the OA content also increased by 57% ± 12%, 243% ± 27%, 300% ± 34%, 400% ± 45% and 471% ± 67%, respectively, after 3, 6, 10, 20 and 24 h of incubation with 0.3 mM OA (Figure 1B). These data suggested that FA uptake was elevated by FA treatment in SH-SY5Y cells. The treated FAs, including PA and OA, were incorporated into SH-SY5Y cells from the medium and reached significant levels after 3 h of incubation.

Bottom Line: We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells.Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease.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.

View Article: PubMed Central - PubMed

Affiliation: Department of School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. m507100009@tmu.edu.tw.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus