Limits...
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

Nicotine antagonizes Aβ25–35-induced pERK1/2 and EGR-1 activation in the hippocampus.C57/BL/L6 mice were injected with Aβ25–35 or control sodium chloride into hippocampus by stereotaxis injection, the mice were then injected 0.15 mg/kg nicotine using a subcutaneous injection twice a day for 2 weeks. Identical doses of sodium chloride were administered as control. After treatment, the mice were sacrificed and the brain were removed for immunostaining for pERK1/2 and EGR-1. The representive figures of immunostaining activity of pERK1/2 and EGR-1 in CA1 regoin were presented in panel a and b respectivily; the quanfication of pERK1/2 and EGR-1 immunoactivity were shown under the figures.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4376385&req=5

pone.0120267.g006: Nicotine antagonizes Aβ25–35-induced pERK1/2 and EGR-1 activation in the hippocampus.C57/BL/L6 mice were injected with Aβ25–35 or control sodium chloride into hippocampus by stereotaxis injection, the mice were then injected 0.15 mg/kg nicotine using a subcutaneous injection twice a day for 2 weeks. Identical doses of sodium chloride were administered as control. After treatment, the mice were sacrificed and the brain were removed for immunostaining for pERK1/2 and EGR-1. The representive figures of immunostaining activity of pERK1/2 and EGR-1 in CA1 regoin were presented in panel a and b respectivily; the quanfication of pERK1/2 and EGR-1 immunoactivity were shown under the figures.

Mentions: The in vitro data provided the hint that nicotine could protect the amyloid neuronal toxicity by regulating EGR-1. We next explore this effect in vivo. As mentioned above in the methods, after treatment, all the mice in four groups were sacrificed by anesthesia. The mice brains were collected for cryosection, the expression of EGR-1 and pERK1/2 were immunostained in CA1 area of hippocampus and cortex. As shown in Fig. 6A, Aβ25–35 loading increased the ERK1/2 phosphorylation in CA1, while nicotine was an antagonist to Aβ25–35-induced the level of pERK1/2. The immunostaining activity of EGR-1 was also increased by injection Aβ25–35 in CA1 area and cortex. After the mice receiving nicotine treatment, the up-regulation of EGR-1 in AD mice model was attenuated (Fig. 6B). The software of Image-pro plus 6.0 was used to analyze the immunoactivity of EGF-1 and pERK1/2, and the quantifications were also presented in Fig. 6 respectively. This data suggested that extracellular signal-regulated kinase was an important signaling molecule in synaptic plasticity and memory [28], indicating that signal transmission in hippocampus was essential for the activation of ERK1/2.


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)

Nicotine antagonizes Aβ25–35-induced pERK1/2 and EGR-1 activation in the hippocampus.C57/BL/L6 mice were injected with Aβ25–35 or control sodium chloride into hippocampus by stereotaxis injection, the mice were then injected 0.15 mg/kg nicotine using a subcutaneous injection twice a day for 2 weeks. Identical doses of sodium chloride were administered as control. After treatment, the mice were sacrificed and the brain were removed for immunostaining for pERK1/2 and EGR-1. The representive figures of immunostaining activity of pERK1/2 and EGR-1 in CA1 regoin were presented in panel a and b respectivily; the quanfication of pERK1/2 and EGR-1 immunoactivity were shown under the figures.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120267.g006: Nicotine antagonizes Aβ25–35-induced pERK1/2 and EGR-1 activation in the hippocampus.C57/BL/L6 mice were injected with Aβ25–35 or control sodium chloride into hippocampus by stereotaxis injection, the mice were then injected 0.15 mg/kg nicotine using a subcutaneous injection twice a day for 2 weeks. Identical doses of sodium chloride were administered as control. After treatment, the mice were sacrificed and the brain were removed for immunostaining for pERK1/2 and EGR-1. The representive figures of immunostaining activity of pERK1/2 and EGR-1 in CA1 regoin were presented in panel a and b respectivily; the quanfication of pERK1/2 and EGR-1 immunoactivity were shown under the figures.
Mentions: The in vitro data provided the hint that nicotine could protect the amyloid neuronal toxicity by regulating EGR-1. We next explore this effect in vivo. As mentioned above in the methods, after treatment, all the mice in four groups were sacrificed by anesthesia. The mice brains were collected for cryosection, the expression of EGR-1 and pERK1/2 were immunostained in CA1 area of hippocampus and cortex. As shown in Fig. 6A, Aβ25–35 loading increased the ERK1/2 phosphorylation in CA1, while nicotine was an antagonist to Aβ25–35-induced the level of pERK1/2. The immunostaining activity of EGR-1 was also increased by injection Aβ25–35 in CA1 area and cortex. After the mice receiving nicotine treatment, the up-regulation of EGR-1 in AD mice model was attenuated (Fig. 6B). The software of Image-pro plus 6.0 was used to analyze the immunoactivity of EGF-1 and pERK1/2, and the quantifications were also presented in Fig. 6 respectively. This data suggested that extracellular signal-regulated kinase was an important signaling molecule in synaptic plasticity and memory [28], indicating that signal transmission in hippocampus was essential for the activation of ERK1/2.

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