TY - JOUR
T1 - Leptin reduces gentamicin-induced apoptosis in rat renal tubular cells via the PI3K-Akt signaling pathway
AU - Chen, Yen Cheng
AU - Chen, Cheng Hsien
AU - Hsu, Yung Ho
AU - Chen, Tso Hsiao
AU - Sue, Yuh Mou
AU - Cheng, Chung Yi
AU - Chen, Tzen-Wen
PY - 2011/5/11
Y1 - 2011/5/11
N2 - Leptin, a circulating hormone secreted mainly from adipose tissues, possesses protective effects on many cell types. Serum leptin concentration increases in patients with chronic renal failure and those undergoing maintenance dialysis. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. In the present study, we intended to investigate the influence of leptin on apoptotic pathways and its mechanism in rat renal tubular cells treated with gentamicin. By using Annexin V-FITC/propidium iodide double staining, we found that leptin expressed a dose-dependent protective effect against gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) within 24 h. Pretreatment of the cells with 50 or 100 ng/ml of leptin induced Bcl-2 and Bcl-xL, increased the phosphorylation of Bad, and decreased the cleaved caspase-3 and caspase-9 in gentamicin-treated NRK-52E cells. Leptin also suppressed the activation of the transcription factor NF-κB and upregulated Akt activation in gentamicin-treated NRK-52E cells. We found that leptin activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway as demonstrated by the suppression of the anti-apoptotic effect of leptin by wortmannin. The treatment of wortmannin suppressed the leptin-induced phospho-Akt, Bcl-2, phospho-Bad as well as Bcl-xL, and recovered the leptin-reduced cleaved caspase-3 and caspase-9. Based on our results, we suggested that leptin can attenuate gentamicin-induced apoptotic injury in rat renal tubular cells through PI3K/Akt signaling pathway.
AB - Leptin, a circulating hormone secreted mainly from adipose tissues, possesses protective effects on many cell types. Serum leptin concentration increases in patients with chronic renal failure and those undergoing maintenance dialysis. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. In the present study, we intended to investigate the influence of leptin on apoptotic pathways and its mechanism in rat renal tubular cells treated with gentamicin. By using Annexin V-FITC/propidium iodide double staining, we found that leptin expressed a dose-dependent protective effect against gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) within 24 h. Pretreatment of the cells with 50 or 100 ng/ml of leptin induced Bcl-2 and Bcl-xL, increased the phosphorylation of Bad, and decreased the cleaved caspase-3 and caspase-9 in gentamicin-treated NRK-52E cells. Leptin also suppressed the activation of the transcription factor NF-κB and upregulated Akt activation in gentamicin-treated NRK-52E cells. We found that leptin activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway as demonstrated by the suppression of the anti-apoptotic effect of leptin by wortmannin. The treatment of wortmannin suppressed the leptin-induced phospho-Akt, Bcl-2, phospho-Bad as well as Bcl-xL, and recovered the leptin-reduced cleaved caspase-3 and caspase-9. Based on our results, we suggested that leptin can attenuate gentamicin-induced apoptotic injury in rat renal tubular cells through PI3K/Akt signaling pathway.
KW - Akt
KW - Apoptosis
KW - Gentamicin
KW - Leptin
KW - Renal tubular cells
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U2 - 10.1016/j.ejphar.2011.02.025
DO - 10.1016/j.ejphar.2011.02.025
M3 - Article
C2 - 21371463
AN - SCOPUS:79953788898
SN - 0014-2999
VL - 658
SP - 213
EP - 218
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -