title: Effect of the PGD2-DP signaling pathway on primary cultured rat hippocampal neuron injury caused by aluminum overload.
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.
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Mai
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Guojuan
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D006827:Hydantoins / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000633:toxicity*; D015230:Prostaglandin D2 / Q000378:metabolism*; D011753:Pyrones / Q000633:toxicity*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C533609:CAY 10471; D002227:Carbazoles; D006827:Hydantoins; D009942:Organometallic Compounds; D011753:Pyrones; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C058848:BW A868C; C067527:aluminum maltolate; D007770:L-Lactate Dehydrogenase; D015230:Prostaglandin D2; D002118:Calcium