镉诱导肾细胞凋亡及其对PI3K/Akt和ERK1/2信号通路的影响

Cadmium-induced apoptosis on LLC-PK_1 cells by activating PI3K / Akt and ERK1 / 2 pathway

目的镉(Cd)诱导猪肾近曲小管上皮细胞(LLC-PK1)凋亡及其对胞内蛋白激酶B(PI3K/Akt)和胞外信号调节激酶(ERK1/2)表达的影响。方法应用不同浓度Cd(0、10、20、40、50μmol/L)作用LLC-PK112 h和40μmol/L Cd作用LLC-PK1不同时间(0、3、6、12、24 h),采用蛋白免疫印迹法检测细胞内蛋白激酶B(PI3K/Akt)和胞外信号调节激酶(ERK1/2)及其磷酸化蛋白表达水平。结果镉可上调PI3K/Akt和ERK1/2的表达;当加入N-乙酰半胱氨酸(NAC)预处理后对镉引起的ERK1/2上调具有抑制作用,但对镉引起的PI3K/Akt上调的抑制作用不明显。结论镉诱导肾细胞凋亡可能与活化PI3K/Akt和ERK1/2通路有关,NAC拮抗镉性肾细胞凋亡的机制可能与抑制镉引起的ERK1/2表达上调有关。

Objective To study the effect of cadmium-induced apoptosis on the activation of PI3K/Akt and ERK1/2 pathway in LLC-PK： cells. Methods After LLC-PK： cells were incubated with cadmium at different concentrations and 40 μmol/L cadmium at various hours.The levels of p-Akt and Akt, p-ERK1/2 and ERK1/2 were determined by Western-blot. Results The phosphorylation of Akt and ERK1/2 was increased after the exposure to cadmium at different concentrations and times. The phosphorylation of ERK1/2 was suppressed by the pretreatment with a free radical scavenger N-acetyl-L-cysteine （NAC）. Conclusions Cadmium-induced apoptosis is associated with the activation of PI3K/Akt and ERK1/2 pathway.We conclude that NAC suppressed cadmium-induced apoptosis by down-regulation of ERK1/2 expression.