Albumin-induced rat tubular cell apoptosis and MAPKs signal transduction / 中华肾脏病杂志

Objective To evaluate the role of albumin and the involvement of mitogenactivated protein kinases(MAPKs) in rat tubular cells apoptosis. Methods Rat tubular cells (NRK-52E) were incubated with various concentrations (10, 20, 30 mg/ml) of delipidated, endotoxin-free bovine serum albumin(BSA) for 6, 12, 18 and 24 h, respectively. The process of apoptosis was evaluated by fluorescence microscope, transmission electron microscope, scanning electron microscope, confocal laser scanning microscope (CLSM) and flow cytometry. To assess the roles of p38, and the activities of JNK and ERK in albumin-induced apoptosis, SB202190 (20 ?mol/L, p38 inhibitor), SP600125 (10 ?mol/L, JNK inhibitor) or PD98059 (20?mol/L, ERK inhibitor) were added to the NRK-52E cells separately in the presence of albumin for 24 hours. Activities of p38, JNK and ERK were assessed by Western blot analyses. Results The albumin induced tubular cell apoptosis in a doseand time-dependent manner. Albumin stimulated the expression of p38 and JNK, whereas it inhibited the expression of ERK. SB202190 and SP600125 ameliorated tubular cells apoptosis but PD980S9 treatment enhanced their apoptosis. Conclusions Albumin induces tabular cell apoptosis in a time- and dose-dependent manner in vitro, transducted through activation of p38 and JNK, and inhibition of ERK.

Angiotensin Ⅱ-induced podocyte apoptosis:Role of the MAPK subtypes / 北京大学学报(医学版)

Objective: To evaluate the role of the MAPK subtypes (p38MAPK, ERK and JNK) in ANG Ⅱ induced apoptosis of cultured human podocytes. Methods: The cultured podocytes were incubated in media containing either vehicle, SB202190(5 ?mol/L, an inhibitor of p38MAPK), PD98059 (1 ?mol/L, an inhibitor of ERK), SP600125 (5 ?mol/L, an inhibitor of JNK), ANG Ⅱ (10 -8 mol/L) with or without SB202190、PD98059 and SP600125 for 18 hours; the cells were assayed for apoptosis by morphologic staining with H 33342 and propidium iodide and DNA fragmentation assays; the cell proteins were probed for phosphorylated MAPKs to determine the activation of specific MAPK subtypes. Results: ANG Ⅱ promoted podocyte apoptosis in a time and dose dependent manner; ANG Ⅱ stimulated p38MAPK, but inhibited JNK; SB202190 inhibited both ANG Ⅱ induced podocyte apoptosis and p38MAPK phosphorylation; Inhibition of ERK by PD98059 had no effect on ANG Ⅱ induced cell apoptosis. Conclusion: ANG Ⅱ induced apoptosis through stimulation of p38MAPK and inhibition of JNK in human podocytes.