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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lee KE,Kim EY,Kim CS,Choi JS,Bae EH,Ma SK,Park JS,Jung YD,Kim SH,Lee JU,Kim SWdoi
10.1016/j.ejphar.2013.05.006subject
Has Abstractpub_date
2013-09-05 00:00:00pages
304-11issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00383-Xjournal_volume
715pub_type
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00053-n
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