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Effect Of Oleic Acid On Aquaglyceroporin3and9Expresssions In HepG2and The Molecular Mechanisms Of Regulating Related Signal Conduct

Posted on:2014-02-07Degree:MasterType:Thesis
Country:ChinaCandidate:L Y GuFull Text:PDF
GTID:2254330425454678Subject:Internal Medicine
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Objective To explore the effect of PI3K/Akt and MAPK signalingpathway on expression of aquaglyceroporin3and aquaglyceroporin9in anoleic acid-induced hepatocyte steatosis model. Methods HepG2cells wereinduced with oleic acid at different concentrations to establish anonalcoholic hepatocyte steatosis model. Oil red O staining and OD valueswere measured to assess the extent of hepatocyte steatosis. Expressions ofAQP3and AQP9in steatosis of HepG2cells were detected with PR-PCRand Western blotting. After treated with PI3K inhibitor LY294004, MAPKinhibitors PD98059, SB230580, SP600125and oleic acid respectively,AQP3and AQP9expressions were measured to analysis the role ofPI3K/Akt and MAPK signaling transduction pathway on regulating AQPs innonalcoholic hepatocyte steatosis. Results Oil red O staining and OD valuesmeasurement showed that hepatocyte steatosis aggravated with thestimulating concentrations. Oleic acid, in a concentration-dependent manner,down-regulated the expression of AQP3and up-regulated AQP9.Theinhibitory effects of oleic acid on AQP3expression decreased only after SB230580treatment. However, incubated with the selective inhibitor ofPI3K (LY294004) and p38(SB230580), the stimulate effects of oleic acid onAQP9expression increased and decreased separately. The expressions ofAQP3and AQP9were not change significantly by blocking ERK1/2andJNK signaling transduction pathway. Further study showed that oleic acidcould inhibit and stimulate the level of Akt and p38phosphorylation,respectively. Conclusion Oleic acid treatment inhibited the expressions ofAQP3and stimulated AQP9in a concentration-dependent manner. ThePI3K/Akt and p38MAPK signaling pathways, but not ERK1/2and JNKsignaling pathway, were involved in the mechanism.
Keywords/Search Tags:aquaglyceroporin3, aquaglyceroporin9, nonalcoholicfatty liver disease, phosphatidylinositol3-kianse, mitogen-actcvated proteinkinases
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