| Title |
Anti-inflammatory Effect of AZD6244 on Acrolein-Induced Neuroinflammation
|
|---|---|
| Published in |
Molecular Neurobiology, November 2019
|
| DOI | 10.1007/s12035-019-01758-8 |
| Pubmed ID | |
| Authors |
Wen-Chien Ho, Chia-Chi Hsu, Hui-Ju Huang, Hsiang-Tsui Wang, Anya Maan-Yuh Lin |
| Abstract |
Clinically, high levels of acrolein (a highly reactive α, β-unsaturated aldehyde) and acrolein adducts are detected in the brain of patients with CNS neurodegenerative diseases, including Alzheimer's disease and spinal cord injury. Our previous study supports this notion by showing acrolein as a neurotoxin in a Parkinsonian animal model. In the present study, the effect of AZD6244 (an ATP non-competitive MEK1/2 inhibitor) on acrolein-induced neuroinflammation was investigated using BV-2 cells and primary cultured microglia. Our immunostaining study showed that lipopolysaccharide (LPS, an inflammation inducer as a positive control) increased co-localized immunoreactivities of phosphorylated ERK and ED-1 (a biomarker of activated microglia) in the treated BV-2 cells. Similar elevation in co-localized immunoreactivities of phosphorylated ERK and ED-1 was detected in the acrolein-treated BV-2 cells. Furthermore, Western blot assay showed increases in phosphorylated ERK in BV-2 cells subjected to LPS (1 μg/mL) or acrolein (30 μM); these increases were blocked by AZD6244 (10 μM). At the same time, AZD6244 attenuated LPS-induced TNF-α (a pro-inflammatory cytokine) and cyclooxygenase-II (COX II, a pro-inflammatory enzyme). Consistently, AZD6244 reduced acrolein-induced elevations in COX-II mRNA and COX-II protein expression. In addition, AZD6244 inhibited acrolein-induced increases in activated caspase 1 (a biomarker of inflammasome activation) and heme oxygenase-1 (a redox-regulated chaperone protein) in BV-2 cells. Using a transwell migration assay, AZD6244 attenuated acrolein (5 μM)-induced migration of BV-2 cells and primary cultured microglia. In conclusion, our study shows that acrolein is capable of inducing neuroinflammation which involved ERK activation in microglia. Furthermore, AZD6244 is capable of inhibiting acrolein-induced neuroinflammation. Our study suggests that ERK inhibition may be a neuroprotective target against acrolein-induced neuroinflammation in the CNS neurodegenerative diseases. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 22% |
| Researcher | 3 | 17% |
| Student > Ph. D. Student | 1 | 6% |
| Other | 1 | 6% |
| Professor > Associate Professor | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 7 | 39% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 28% |
| Neuroscience | 2 | 11% |
| Biochemistry, Genetics and Molecular Biology | 1 | 6% |
| Nursing and Health Professions | 1 | 6% |
| Unknown | 9 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 December 2019.
All research outputs
#18,040,081
of 23,177,498 outputs
Outputs from Molecular Neurobiology
#2,359
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Outputs of similar age
#318,697
of 459,330 outputs
Outputs of similar age from Molecular Neurobiology
#55
of 71 outputs
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