镉诱导肾细胞凋亡及其对P13K／Akt和ERK1／2信号通路的影响

目的镉（cd）诱导猪肾近曲小管上皮细胞（LLC-PK）凋亡及其对胞内蛋白激酶B（P13K／Akt）和胞外信号调节激酶（ERKI／2）表达的影响。方法应用不同浓度Cd（0、10、20、40、50μmol／L）作用LLC-PK：12h和40μmol／Lcd作用LLC-PK。不同时间（0、3、6、12、24h），采用蛋白免疫印迹法检测细胞内蛋白激酶B（P13K／Akt）和胞外信号调节激酶（ERKl／2）及其磷酸化蛋白表达水平。结果镉可上调P13K／Akt和ERKl／2的表达：当加入N-乙酰半胱氨酸（NAC）预处理后对镉引起的ERKl／2上调具有抑制作用，但对镉引起的P13K／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P13K／Akt和ERKI／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ERKl／2表达上调有关。

Cadmium-induced apoptosis on LLC-PK1 cells by activating PI3K/Akt and ERK1/2 pathway

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.