title: Curcumin regulates peroxisome proliferator-activated receptor-γ coactivator-1α expression by AMPK pathway in hepatic stellate cells in vitro.
abstract: Curcumin exerts an inhibitory effect on hepatic stellate cell (HSC) activation, a key step for liver fibrogenesis, and on liver fibrosis by up-regulation of peroxisome proliferator-activated receptor-γ (PPARγ) expression. PPARγ plays a crucial role in suppression of HSC activation. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) functions as a co-activator for PPARγ. Therefore, researches on the effect of curcumin on PGC-1α might contribute to understanding of the mechanisms underlying curcumin inhibition of HSC activation and liver fibrosis through PPARγ. The present study aimed to investigate the effect of curcumin on PGC-1α expression in HSCs in vitro and examine the underlying molecular mechanisms by western blot, reat-time PCR, and transfection. Our results showed that curcumin stimulation increased PGC-1α expression and the effects of curcumin on PGC-1α expression were correlated with the activation of adenosine monophosphate-activated protein kinase (AMPK). Curcumin increased superoxide dimutase-2 (SOD2) transcription and activity by AMPK/PGC-1α axis. Moreover, PGC-1α was demonstrated to inhibit α1(I) collagen (a marker for liver fibrosis) transcription in cultured HSCs. These results demonstrated the promotion effect of curcumin on PGC-1α expression through AMPK pathway, which led to the increases in PPARγ activity and in SOD-2 transcription and activity. These data might suggest a possible new explanation for the inhibitory effect of curcumin on HSC activation and on liver fibrogenesis.
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Qi xiou road 19, Nantong 226001, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Qi xiou road 19, Nantong 226001, Jiangsu, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China. Electronic address: yajunzhou97127@yahoo.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D000099156:Superoxide Dismutase 2
chemical_list: D055372:AMP-Activated Protein Kinases; D024042:Collagen Type I; D003474:Curcumin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C501429:Ppargc1a protein, rat
keywords: Adenosine monophosphate-activated protein kinase; Curcumin; Curcumin (PubChem CID: 969516); Hepatic stellate cell; Peroxisome proliferator-activated receptor-γ; Peroxisome proliferator-activated receptor-γ coactivator-1α