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Mechanisms Involved in the Antiplatelet Activity of Highly Oxidized Low Density Lipoprotein in Human Platelets
The intracellular mechanisms underlying oxidized low-density lipoprotein-signaling pathways in platelets remained obscure and findings had been Glutamate receptors (GluRs) are known to mediate intracellular calcium elevation through receptor ion channels or coupling to second messenger pathways. Knowing their calcium regulation in early developing neurons may provide important clues for their developmental roles. In this study, we used early developing neurons differentiated from embryonic stem cell P19 cell line to investigate GluR-mediated intracellular calcium surge, expression of growth factor receptors and programmed cell death during neuronal development. Results are summarized as following. (1) The expression of the AMPA receptor subunit GluR2/3 appeared at the same stage as the beginning of neurogenesis. (2) The expression of the KA receptor subunit GluR5/6/7 appeared as early as in the stem cell stage, decreased during differentiation, and increased toward neuronal maturation. (3) In 5DAR P19 neurons, mGluR1 receptor also expressed on the membrane. (4) Specific GluR agonists KA, AMPA, NMDA had no increase of [Ca2+]i changes in 3DAR P19-derived neurons until 5DAR and 7DAR, whereas trans-ACPD had no effect at 7DAR. (5) EAAs resulted in induction of p53 and Bax protein expression in 5DAR P19 neurons. Other than KA, all EAAs were resulted in reduction of Bcl-2 expression. And the expression of TrkA receptors were induced by all EAAs. (6) Glutamate had no effect on apoptosis of P19 neurons, but following NGF treatment, all EAAs could reduce their apoptosis. These results were also be proved by Western blot analysis, and EAA may cooperate with NGF on regulating neuronal differentiation and survival. These results suggest that glutamate receptors are not only acting differently in terms of mediating [Ca2+]i, but also regulating apoptotic or antiapoptotic protein and NGF receptor expression. The glutamate receptor-mediated profound decreased of p53 and Bax protein expression; induced Bcl-2 and TrkA expression by glutamate receptor agonists implies the EAA-mediated cell protection may play an important role in neural development.