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Macrophage-stimulating protein attenuates hydrogen peroxide-induced apoptosis in human renal HK-2 cells.
- Source :
-
European Journal of Pharmacology . Sep2013, Vol. 715 Issue 1-3, p304-311. 8p. - Publication Year :
- 2013
-
Abstract
- Abstract: Macrophage-stimulating protein (MSP) and its receptor, recepteur d’origine nantais (RON), play an important role in cell proliferation and migration. We have investigated the role of MSP in hydrogen peroxide (H2O2)-induced renal tubular apoptosis. Human renal proximal tubular (HK-2) cells were incubated with H2O2 for 24h in the presence of different concentrations of MSP, and cell viability was measured by MTT assay. The protein expression of Bax, Bcl-2, caspase-3, mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-κB) was determined by semiquantitative immunoblotting. Apoptosis was assessed by flow cytometry analysis after HK-2 cells were stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. H2O2 treatment decreased cell viability in HK-2 cells; this was counteracted by MSP pretreatment. H2O2 treatment induced an increased ratio of Bax/Bcl-2, cleaved caspase-3, and the number of condensed nuclei, which was also counteracted by MSP. Flow cytometry analysis showed H2O2-induced apoptosis, and its prevention by MSP treatment. Increased protein expression of phospho-p38 MAPK was attenuated by MSP, while phospho-extracellular signal-regulated kinase and c-Jun-N-terminal kinase were not affected. H2O2 induced NF-κB activation and IκB-α degradation, but the increased nuclear NF-κB activation was counteracted by MSP or by a p38 MAPK inhibitor. H2O2 treatment decreased expression of phospho-PI3K and phospho-Akt, which was reversed by MSP pretreatment. These findings suggest that MSP attenuates H2O2-induced apoptosis in HK-2 cells by modulating the p38 and NF-κB, as well as PI3K/Akt, signaling pathways. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 715
- Issue :
- 1-3
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 89998464
- Full Text :
- https://doi.org/10.1016/j.ejphar.2013.05.006