不同浓度β-淀粉样蛋白寡聚体的毒性差异

Different neurotoxicities of different concentrations of oligomeric amyloid beta

目的探讨不同浓度的β淀粉样蛋白(amyloid beta,Aβ)寡聚体毒性的差异。方法 0.5μmol/L,1μmol/L,1.5μmol/L,2μmol/L,2.5μmol/L,3μmol/L的Aβ1-42寡聚体(A-βderived diffusible ligands,ADDLs)处理PC12细胞(大鼠肾上腺嗜铬细胞瘤细胞),western blot检测钙蛋白酶(calpain)的激活程度,蛋白激酶A的催化亚基(catalytic subunits of cAMP-dependent kinase,PKA-C)和磷酸化环磷酸腺苷反应元件结合蛋白(phosphory lated cAMP response element binding protein,pCREB)的表达水平。结果所有浓度的ADDLs均导致pCREB的下降(P<0.05),但均未影响PKA-C的含量(P>0.05)。0.5μmol/L,1μmol/L,1.5μmol/L的ADDLs导致pCREB的下降与calpain的激活无关,而2μmol/L,2.5μmol/L,3μmol/L的ADDLs导致pCREB的下降与calpain激活有关。结论不同浓度ADDLs通过不同毒性通路导致pCREB下降:高浓度的ADDLs通过激活calpain,而低浓度ADDLs则可能通过其他途径,但两者均未通过影响PKA-C的含量来降低pCREB水平。

Objective To investigate the different neurotoxities of different concentrations of oligomeric amyloid beta.Methods PC12 cells were treated with 0.5 μmol/L,1 μmol/L,1.5 μmol/L,2 μmol/L,2.5 μmol/L and 3 μmol/L Aβ1-42 oligomers（Aβ-derived diffusible ligands,ADDLs）.The activation of calpain and protein level of catalytic subunits of PKA（PKA-C） and phosphorylated cAMP response element binding protein（pCREB） were analysed by western blot.Results All concentrations of ADDLs could decrease pCREB（P0.05）,but had no impact on PKA-C levels（P0.05）.While 2 μmol/L,2.5 μmol/L and 3 μmol/L ADDLs decreased pCREB through activation of calpain,0.5 μmol/L,1 μmol/L and 1.5 μmol/L ADDLs decreased pCREB through other mechanisms.Conclusions Different concentrations of ADDLs decreased pCREB though different ways： high concentrations through activation of calpain,while low concentrations through other mechanisms.However,neither decreased pCREB levels through impact on the levels of PKA-C.