麩胺酸受體在神經分化過程中所扮演的角色
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麩胺酸受體在神經分化過程中所扮演的角色 PowerPoint PPT Presentation


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麩胺酸受體在神經分化過程中所扮演的角色.

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麩胺酸受體在神經分化過程中所扮演的角色

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4150679

麩胺酸受體在神經分化過程中所扮演的角色

  • 氧化低密度脂蛋白對於血小板的細胞內訊息路徑尚未完全知曉,其過去的發現是具爭議性的。因此本實驗的目的在探討氧化低密度脂蛋白麩胺酸受體可藉由受體離子通道,或連接次級訊息傳遞路徑,而造成細胞內鈣離子濃度的上升;所以了解在發育早期神經元中,麩胺酸受體對鈣離子的調控作用,對於探討其在神經發育過程中所扮演的角色是很重要的。在本篇論文的研究主題中,我們利用源自胚胎的幹細胞,P19所分化而來的發育早期的神經細胞,來研究神經發育期中,麩胺酸受體所引發的細胞內鈣離子濃度的上升,及他們對生長因子受體的表現與細胞的計劃性死亡之影響。結果如下: (1) AMPA受體的次單位 (subunits) 麩胺酸受2/3 (GluR2/3),在神經細胞開始形成的時期就會有表現。 (2) 紅藻胺酸受體之次單位麩胺酸受體5/6/7 (GluR5/6/7),則是在原始P19幹細胞中即已有表現,其後在神經細胞的分化過程中則逐漸減少,而在神經元成熟之後GluR5/6/7的表現量又會增加。 (3) 而在5DAR的P19神經細胞膜上,也可看到mGluR1受體的表現。 (4) 麩胺酸受體的專一性致效劑 (agonist) KA、AMPA及NMDA,在以維生素A酸處理後的3DAR P19-derived neuron中,並不會影響細胞內鈣離子濃度變化的情形,而一直到5DAR及7DAR時,才會造成細胞內鈣離子濃度的增加;然而,t-ACPD則一直到7DAR時,都不會去影響P19-derived neuron的細胞內鈣離子的濃度。 (5)而在5DAR的P19-derived neuron給予興奮性胺基酸致效劑刺激時,發現會增加細胞內p53與Bax的表現。至於Bcl-2則是除了紅藻胺酸外,其餘的興奮性胺基酸都會減少其表現。而TrkA也會因興奮性胺基酸的作用,而增加其表現。 (6) 麩胺酸致效劑雖不會影響細胞的計劃性死亡,但可以透過與神經生長因子之間的相互作用,使細胞的計劃性死亡降低,這作用亦已經由西方墨點法證實。由以上的實驗結果可知,麩胺酸受體不只會調控細胞內鈣離子濃度的上升,亦因受體subtype的不同而有所差異。同時,他們也會去調節與細胞自殺性死亡相關蛋白質及神經營養因子受體TrkA的表現。由麩胺酸受體的特異性致效劑所導致p53與Bax的減少及Bcl-2與TrkA表現增加,證明了興奮性胺基酸在發育中的神經細胞所具有的保護作用當中,可能扮演著一個相當重要的角色。


4150679

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.


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