PMC:2783367 / 31066-32863
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/2783367","sourcedb":"PMC","sourceid":"2783367","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2783367","text":"Our earlier results demonstrated the roles of curcumin and PPARγ activation in the inhibition of the lox-1 promoter activity and gene expression (Fig. 3-5). Results in Fig. 6 suggested that the TCF/LEF-1 binding site was the curcumin response element, which might mediate the curcumin-caused inhibition of the lox-1 promoter activity. To explore the underlying mechanisms, it is plausible to hypothesize that the curcumin-activated PPARγ interrupted canonical Wnt signaling, leading to the reduction in the lox-1 promoter activity and to the inhibition of lox-1 expression in HSCs. To test the hypothesis, HSCs were co-transfected with the plasmid pLOX-1-Luc, or the mutant plasmid pLOX-1(mut)-Luc, and the PPARγ cDNA expression plasmid pPPARγ or the empty control vector pcDNA. After recovery, cells were cultured for 24 hr in DMEM with FBS (10%), which contained enough agonists to activate PPARγ in HSCs 19, 23, 24. Luciferase activity assays in Fig. 7A demonstrated that forced expression of PPARγ from pPPARγ significantly reduced luciferase activity by 63.4% in cells co-transfected with the wild-type plasmid pLOX-1-Luc (the upper black column), compared to the empty control vector pcDNA (the upper white column). In great contrast, forced expression of PPARγ from pPPARγ failed to reduce luciferase activity in cells co-transfected with the mutant plasmid pLOX-1(mut)-Luc (the lower black column), compared to the empty control vector pcDNA (the lower white column). Luciferase activity was much lower in cells transfected with pLOX-1(mut)-Luc (the lower white column), compared to that in cells transfected with the wild-type pLOX-1-Luc (the upper white column), confirming the role of the TCF/LEF-1 binding site in controlling the basal activity of the gene promoter observed in Fig. 6.","tracks":[{"project":"2_test","denotations":[{"id":"19736547-10969082-66178368","span":{"begin":907,"end":909},"obj":"10969082"},{"id":"19736547-10969082-66178368","span":{"begin":907,"end":909},"obj":"10969082"},{"id":"19736547-12660143-66178369","span":{"begin":911,"end":913},"obj":"12660143"},{"id":"19736547-12660143-66178369","span":{"begin":911,"end":913},"obj":"12660143"},{"id":"19736547-15320868-66178370","span":{"begin":915,"end":917},"obj":"15320868"},{"id":"19736547-15320868-66178370","span":{"begin":915,"end":917},"obj":"15320868"},{"id":"T37876","span":{"begin":907,"end":909},"obj":"10969082"},{"id":"T58830","span":{"begin":907,"end":909},"obj":"10969082"},{"id":"T74270","span":{"begin":911,"end":913},"obj":"12660143"},{"id":"T4930","span":{"begin":911,"end":913},"obj":"12660143"},{"id":"T23770","span":{"begin":915,"end":917},"obj":"15320868"},{"id":"T2549","span":{"begin":915,"end":917},"obj":"15320868"}],"attributes":[{"subj":"19736547-10969082-66178368","pred":"source","obj":"2_test"},{"subj":"19736547-10969082-66178368","pred":"source","obj":"2_test"},{"subj":"19736547-12660143-66178369","pred":"source","obj":"2_test"},{"subj":"19736547-12660143-66178369","pred":"source","obj":"2_test"},{"subj":"19736547-15320868-66178370","pred":"source","obj":"2_test"},{"subj":"19736547-15320868-66178370","pred":"source","obj":"2_test"},{"subj":"T37876","pred":"source","obj":"2_test"},{"subj":"T58830","pred":"source","obj":"2_test"},{"subj":"T74270","pred":"source","obj":"2_test"},{"subj":"T4930","pred":"source","obj":"2_test"},{"subj":"T23770","pred":"source","obj":"2_test"},{"subj":"T2549","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecac93","default":true}]}]}}