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Low dose nicotine attenuates Aβ neurotoxicity through activation early growth response gene 1 pathway.

Xue M, Zhu L, Zhang J, Qiu J, Du G, Qiao Z, Jin G, Gao F, Zhang Q - PLoS ONE (2015)

Bottom Line: In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity.Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35).This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Institute of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, Fujian, 361005, P.R.China.

ABSTRACT
Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity. Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35). This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.

No MeSH data available.


Related in: MedlinePlus

EGR-1 upregulates CyclinD1.a) SH-SY5Y cells were treated with nicotine for 45 min. CyclinD1 and its phosphorylation were detected by Western blotting. b) In SH-SY5Y cell line, the EGR-1 was blocked. c) Lane 3 and lane 4 are different from lane 1 and lane 2, which were treated with 10–6 M nicotine for 45 min. d) Following the overexpression of EGR-1 in SH-SY5Y cell line, the cyclinD1 and its phosphorylation were detected.
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pone.0120267.g005: EGR-1 upregulates CyclinD1.a) SH-SY5Y cells were treated with nicotine for 45 min. CyclinD1 and its phosphorylation were detected by Western blotting. b) In SH-SY5Y cell line, the EGR-1 was blocked. c) Lane 3 and lane 4 are different from lane 1 and lane 2, which were treated with 10–6 M nicotine for 45 min. d) Following the overexpression of EGR-1 in SH-SY5Y cell line, the cyclinD1 and its phosphorylation were detected.

Mentions: The above data suggested that EGR-1 be in vital for the neuroprotective effect of nicotine in Aβ-induced cytotoxicity in SH-SY5Y. Since EGR-1 is an important transcriptional factor, we then wondered which EGR-1 downstream gene was involved. CyclinD1 drew our attention. When SH-SY5Y cell line was treated by nicotine, the CyclinD1 was up-regulated (Fig. 5A). In the absent of EGR-1 by shRNA knockdown, the up-regulation of CyclinD1 by nicotine was reduced (Fig. 5B and 5C). With extra EGR-1 overexpression, CyclinD1 and its phosphorylation were significantly increased (Fig. 5D). It was hypothesized that EGR-1 might regulate CyclinD1 against Aβ25–35-induced cytotoxicity.


Low dose nicotine attenuates Aβ neurotoxicity through activation early growth response gene 1 pathway.

Xue M, Zhu L, Zhang J, Qiu J, Du G, Qiao Z, Jin G, Gao F, Zhang Q - PLoS ONE (2015)

EGR-1 upregulates CyclinD1.a) SH-SY5Y cells were treated with nicotine for 45 min. CyclinD1 and its phosphorylation were detected by Western blotting. b) In SH-SY5Y cell line, the EGR-1 was blocked. c) Lane 3 and lane 4 are different from lane 1 and lane 2, which were treated with 10–6 M nicotine for 45 min. d) Following the overexpression of EGR-1 in SH-SY5Y cell line, the cyclinD1 and its phosphorylation were detected.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376385&req=5

pone.0120267.g005: EGR-1 upregulates CyclinD1.a) SH-SY5Y cells were treated with nicotine for 45 min. CyclinD1 and its phosphorylation were detected by Western blotting. b) In SH-SY5Y cell line, the EGR-1 was blocked. c) Lane 3 and lane 4 are different from lane 1 and lane 2, which were treated with 10–6 M nicotine for 45 min. d) Following the overexpression of EGR-1 in SH-SY5Y cell line, the cyclinD1 and its phosphorylation were detected.
Mentions: The above data suggested that EGR-1 be in vital for the neuroprotective effect of nicotine in Aβ-induced cytotoxicity in SH-SY5Y. Since EGR-1 is an important transcriptional factor, we then wondered which EGR-1 downstream gene was involved. CyclinD1 drew our attention. When SH-SY5Y cell line was treated by nicotine, the CyclinD1 was up-regulated (Fig. 5A). In the absent of EGR-1 by shRNA knockdown, the up-regulation of CyclinD1 by nicotine was reduced (Fig. 5B and 5C). With extra EGR-1 overexpression, CyclinD1 and its phosphorylation were significantly increased (Fig. 5D). It was hypothesized that EGR-1 might regulate CyclinD1 against Aβ25–35-induced cytotoxicity.

Bottom Line: In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity.Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35).This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Institute of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, Fujian, 361005, P.R.China.

ABSTRACT
Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity. Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35). This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.

No MeSH data available.


Related in: MedlinePlus