同型半胱氨酸对Aβ神经毒性促进作用

EFFECT OF HOMOCYSTEINE ON POTENTIATING ΒETA-AMYLOID NEUROTOXICITY

目的研究同型半胱氨酸是否促进β淀粉样肽(β-amyloid,Aβ)对体外培养海马细胞的神经毒性。方法用同型半胱氨酸和/或Aβ42处理体外培养的海马细胞,观察神经细胞的凋亡情况以及神经细胞内的游离钙浓度的改变、DNA损伤和氧化损伤。结果同型半胱氨酸(250μmol/L)和Aβ42(10μmol/L)同时作用海马细胞的凋亡率显著高于Hcy或Aβ42单独作用,甚至高于两者单独作用之和。Hcy没有促进Aβ42对DNA的作用;在神经兴奋毒和氧化损伤作用方面,同型半胱氨酸(250μmol/L)和Aβ42(10μmol/L)产生了协同作用,同型半胱氨酸可促进Aβ42引发海马细胞内游离钙浓度升高和MDA的产生增多。结论同型半胱氨酸可通过神经兴奋毒作用、氧化损伤和引发凋亡等机制促进Aβ42对体外培养海马细胞的神经毒性作用。

Objective To examine the possibility that homocysteine （Hcy） may augment β-amyloid （Aβ） neurotoxicity. Method Cultured hippocampal neurons were treatd with Hcy and/or Aβ42 and it＇s apoptosis, calcium influx, DNA damage and oxidative injury were examined. Results Combined treatment with 250μmol/L Hcy and 10μmol/L Aβ42 increased the apoptosis rate of hippocampal neurons significantly more than either agent alone, and even the sum of each agent treated alone. The combined treatment significantly exceeded the cytosolic calcium accumulation and MDA obtained with either alone or the sum of each agent. A significant increase in DNA damage also occurred in neurons exposed to Aβ42 in the presence of Hcy, but the magnitude of the increase was not greater than that seen with either treatment alone Conclusion Hcy could potentiate Aβ neurotoxicity by neuron exitotoxicity, oxidative stress and inducingapoptosis.