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Effect of the PGD2-DP signaling pathway on primary cultured rat hippocampal neuron injury caused by aluminum overload.

Ma J, Yang Q, Wei Y, Yang Y, Ji C, Hu X, Mai S, Kuang S, Tian X, Luo Y, Liang G, Yang J - Sci Rep (2016)

Bottom Line: BW245C reduced the Ca(2+) fluorescence intensity and protected the neurons.DK-PGD2 increased the intensity of Ca(2+) fluorescence, while CAY10471 had the opposite effect.In conclusion, contrary to the effect of DP2, the PGD2-DP1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.

ABSTRACT
In the present study, the agonists and antagonists of DP receptor were used to examine whether the PGD2-DP signaling pathway affects neuronal function. Primary cultured hippocampal neuron was prepared and treated with aluminum maltolate (100 μM) to establish the neuronal damage model. PGD2 and cAMP content was detected by ELISA. L-PGDS and DPs mRNA and protein expression were measured by RT-PCR and Western blotting, respectively. The aluminium-load neuron was treated with the DP1 agonist BW245C, the DP1 antagonist BWA868C, the DP2 agonist DK-PGD2, and the DP2 antagonist CAY10471, respectively. Neuronal pathomorphology was observed using H-E staining. The cell viability and the lactate dehydrogenase leakage rates of neurons were measured with MTT and LDH kit, respectively. Ca(2+) level was detected by Fluo-3/AM. In the model group, the MTT values obviously decreased; LDH leakage rates and PGD2 content increased significantly; L-PGDS, DP1 mRNA and protein expressions increased, and DP2 level decreased. BW245C reduced the Ca(2+) fluorescence intensity and protected the neurons. DK-PGD2 increased the intensity of Ca(2+) fluorescence, while CAY10471 had the opposite effect. In conclusion, contrary to the effect of DP2, the PGD2-DP1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.

No MeSH data available.


Related in: MedlinePlus

The change of LDH leakage rate intervened with the DP agonists and antagonists.(a) BW245C and (d) CAY10471 significantly decreased the LDH leakage rate in Al3+-treated groups. (b) BWA868C and (c) DK-PGD2 increased the LDH leakage rate in Al3+-treated groups. Values were mean ± SD of four individual experiments (n = 4. ##P < 0.01 compared with control group. **P < 0.01 compared with Al3+-treated group, one-way ANOVA with Dunnett’s multiple comparisons).
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f6: The change of LDH leakage rate intervened with the DP agonists and antagonists.(a) BW245C and (d) CAY10471 significantly decreased the LDH leakage rate in Al3+-treated groups. (b) BWA868C and (c) DK-PGD2 increased the LDH leakage rate in Al3+-treated groups. Values were mean ± SD of four individual experiments (n = 4. ##P < 0.01 compared with control group. **P < 0.01 compared with Al3+-treated group, one-way ANOVA with Dunnett’s multiple comparisons).

Mentions: Compared with the control group, the solvent control group of primary cultured hippocampal neurons exhibited no considerable change in the LDH leakage rate, while the rate of LDH leakage rose significantly in the Al3+-treated group (P < 0.01). The DP1 agonist (BW245C) blunted the increase of leakage rate of LDH in Al (malt)3 –treated group in a concentration dependent manner (P < 0.01). The DP1 antagonist (BWA868C) of 10−5 M increased significantly the LDH leakage rate in Al (malt)3 –treated group (P < 0.01). The LDH leakage rate was increased significantly when treated with the DP2 agonists (DK-PGD2) at concentration of 10−5 M and 3 × 10−5 M (P < 0.01). The LDH leakage rate reduced significantly when treated with the DP2 antagonist (CAY10471) at different concentrations (10−5, 3 × 10−5 and 10−6 M) (P < 0.01) (Fig. 6).


Effect of the PGD2-DP signaling pathway on primary cultured rat hippocampal neuron injury caused by aluminum overload.

Ma J, Yang Q, Wei Y, Yang Y, Ji C, Hu X, Mai S, Kuang S, Tian X, Luo Y, Liang G, Yang J - Sci Rep (2016)

The change of LDH leakage rate intervened with the DP agonists and antagonists.(a) BW245C and (d) CAY10471 significantly decreased the LDH leakage rate in Al3+-treated groups. (b) BWA868C and (c) DK-PGD2 increased the LDH leakage rate in Al3+-treated groups. Values were mean ± SD of four individual experiments (n = 4. ##P < 0.01 compared with control group. **P < 0.01 compared with Al3+-treated group, one-way ANOVA with Dunnett’s multiple comparisons).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835855&req=5

f6: The change of LDH leakage rate intervened with the DP agonists and antagonists.(a) BW245C and (d) CAY10471 significantly decreased the LDH leakage rate in Al3+-treated groups. (b) BWA868C and (c) DK-PGD2 increased the LDH leakage rate in Al3+-treated groups. Values were mean ± SD of four individual experiments (n = 4. ##P < 0.01 compared with control group. **P < 0.01 compared with Al3+-treated group, one-way ANOVA with Dunnett’s multiple comparisons).
Mentions: Compared with the control group, the solvent control group of primary cultured hippocampal neurons exhibited no considerable change in the LDH leakage rate, while the rate of LDH leakage rose significantly in the Al3+-treated group (P < 0.01). The DP1 agonist (BW245C) blunted the increase of leakage rate of LDH in Al (malt)3 –treated group in a concentration dependent manner (P < 0.01). The DP1 antagonist (BWA868C) of 10−5 M increased significantly the LDH leakage rate in Al (malt)3 –treated group (P < 0.01). The LDH leakage rate was increased significantly when treated with the DP2 agonists (DK-PGD2) at concentration of 10−5 M and 3 × 10−5 M (P < 0.01). The LDH leakage rate reduced significantly when treated with the DP2 antagonist (CAY10471) at different concentrations (10−5, 3 × 10−5 and 10−6 M) (P < 0.01) (Fig. 6).

Bottom Line: BW245C reduced the Ca(2+) fluorescence intensity and protected the neurons.DK-PGD2 increased the intensity of Ca(2+) fluorescence, while CAY10471 had the opposite effect.In conclusion, contrary to the effect of DP2, the PGD2-DP1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.

ABSTRACT
In the present study, the agonists and antagonists of DP receptor were used to examine whether the PGD2-DP signaling pathway affects neuronal function. Primary cultured hippocampal neuron was prepared and treated with aluminum maltolate (100 μM) to establish the neuronal damage model. PGD2 and cAMP content was detected by ELISA. L-PGDS and DPs mRNA and protein expression were measured by RT-PCR and Western blotting, respectively. The aluminium-load neuron was treated with the DP1 agonist BW245C, the DP1 antagonist BWA868C, the DP2 agonist DK-PGD2, and the DP2 antagonist CAY10471, respectively. Neuronal pathomorphology was observed using H-E staining. The cell viability and the lactate dehydrogenase leakage rates of neurons were measured with MTT and LDH kit, respectively. Ca(2+) level was detected by Fluo-3/AM. In the model group, the MTT values obviously decreased; LDH leakage rates and PGD2 content increased significantly; L-PGDS, DP1 mRNA and protein expressions increased, and DP2 level decreased. BW245C reduced the Ca(2+) fluorescence intensity and protected the neurons. DK-PGD2 increased the intensity of Ca(2+) fluorescence, while CAY10471 had the opposite effect. In conclusion, contrary to the effect of DP2, the PGD2-DP1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.

No MeSH data available.


Related in: MedlinePlus