PMC:2783367 / 23415-25393
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":"We have previously reported that curcumin induces expression of endogenous PPARγ gene and stimulates its activity in activated HSCs, which is a prerequisite for curcumin to inhibit HSC activation in vitro23, 24. To elucidate the mechanisms by which curcumin suppressed gene expression of LOX-1 in HSCs, we postulated that PPARγ mediated the inhibitory effect of curcumin on lox-1 expression. To test this postulation, HSCs were transiently transfected with the LOX-1 promoter luciferase reporter pLOX-1-Luc. After recovery, cells were pretreated with or without the PPARγ antagonist PD68235 (20 μM) for 30 min prior to the addition of curcumin at 20 μM for additional 24 hr. As shown in Fig. 4A by luciferase activity assays, compared to the untreated control cells (the 1st column on the left), cells treated with curcumin showed a significant reduction in luciferase activity (the 2nd column), confirming the inhibitory impact of curcumin on the lox-1 promoter activity in HSCs. In great contrast, the pretreatment of cells with the PPARγ antagonist PD68235 abrogated this inhibitory impact of curcumin (the 4th column), suggesting the necessity of the activation of PPARγ in the curcumin-caused inhibition of the lox-1 promoter activity. To verify the observation, HSCs were pretreated with or without PD68235 (20 μM) for 30 min prior to the addition of curcumin (20 μM) for additional 24 hr. Whole cell extracts were prepared for Western blotting analyses. As demonstrated in Fig. 4B, compared to the untreated control (the 1st well), curcumin, as expected, significantly reduced the abundance of LOX-1 in the cells (the 2nd well). The inhibition of the PPARγ activity by the pretreatment with PD68235 apparently eliminated the inhibitory effect of curcumin on the abundance of LOX-1 (the 4th well). These results collectively suggested that the activation of PPARγ might play a critical role in the curcumin-caused inhibition of lox-1 expression in activated HSCs in vitro.","tracks":[{"project":"2_test","denotations":[{"id":"19736547-12660143-66178359","span":{"begin":204,"end":206},"obj":"12660143"},{"id":"19736547-12660143-66178359","span":{"begin":204,"end":206},"obj":"12660143"},{"id":"19736547-15320868-66178360","span":{"begin":208,"end":210},"obj":"15320868"},{"id":"19736547-15320868-66178360","span":{"begin":208,"end":210},"obj":"15320868"},{"id":"T2704","span":{"begin":204,"end":206},"obj":"12660143"},{"id":"T33177","span":{"begin":204,"end":206},"obj":"12660143"},{"id":"T3367","span":{"begin":208,"end":210},"obj":"15320868"},{"id":"T61757","span":{"begin":208,"end":210},"obj":"15320868"}],"attributes":[{"subj":"19736547-12660143-66178359","pred":"source","obj":"2_test"},{"subj":"19736547-12660143-66178359","pred":"source","obj":"2_test"},{"subj":"19736547-15320868-66178360","pred":"source","obj":"2_test"},{"subj":"19736547-15320868-66178360","pred":"source","obj":"2_test"},{"subj":"T2704","pred":"source","obj":"2_test"},{"subj":"T33177","pred":"source","obj":"2_test"},{"subj":"T3367","pred":"source","obj":"2_test"},{"subj":"T61757","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93d9","default":true}]}]}}