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Effects of curcumin on peroxisome proliferator-activated receptor gamma expression and nuclear translocation/redistribution in culture-activated rat hepatic stellate cells.
Chin Med J (Engl). 2007 May 05; 120(9):794-801.CM

Abstract

BACKGROUND

The function of peroxisome proliferator-activated receptor gamma (PPARgamma) in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs) through PPARgamma signaling were investigated.

METHODS

HSCs were isolated from the normal Sprague Dawley rats through in situ perfusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy lsulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARgamma subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay.

RESULTS

Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I. PPARgamma is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.

CONCLUSIONS

Curcumin can inhibit the proliferation and activation of HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2 and MMP-9. The effects of curcumin are mediated through activating the PPARgamma signal transduction pathway and associated with PPARgamma nuclear translocation/redistribution.

Authors+Show Affiliations

Institute of Liver Diseases, Shuguang Hospital, Shanghai University of TCM, Shanghai 201203, China. chengyang@hotmail.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17531121

Citation

Cheng, Yang, et al. "Effects of Curcumin On Peroxisome Proliferator-activated Receptor Gamma Expression and Nuclear Translocation/redistribution in Culture-activated Rat Hepatic Stellate Cells." Chinese Medical Journal, vol. 120, no. 9, 2007, pp. 794-801.
Cheng Y, Ping J, Xu LM. Effects of curcumin on peroxisome proliferator-activated receptor gamma expression and nuclear translocation/redistribution in culture-activated rat hepatic stellate cells. Chin Med J (Engl). 2007;120(9):794-801.
Cheng, Y., Ping, J., & Xu, L. M. (2007). Effects of curcumin on peroxisome proliferator-activated receptor gamma expression and nuclear translocation/redistribution in culture-activated rat hepatic stellate cells. Chinese Medical Journal, 120(9), 794-801.
Cheng Y, Ping J, Xu LM. Effects of Curcumin On Peroxisome Proliferator-activated Receptor Gamma Expression and Nuclear Translocation/redistribution in Culture-activated Rat Hepatic Stellate Cells. Chin Med J (Engl). 2007 May 5;120(9):794-801. PubMed PMID: 17531121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of curcumin on peroxisome proliferator-activated receptor gamma expression and nuclear translocation/redistribution in culture-activated rat hepatic stellate cells. AU - Cheng,Yang, AU - Ping,Jian, AU - Xu,Lie-Ming, PY - 2007/5/29/pubmed PY - 2007/7/21/medline PY - 2007/5/29/entrez SP - 794 EP - 801 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 120 IS - 9 N2 - BACKGROUND: The function of peroxisome proliferator-activated receptor gamma (PPARgamma) in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs) through PPARgamma signaling were investigated. METHODS: HSCs were isolated from the normal Sprague Dawley rats through in situ perfusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy lsulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARgamma subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay. RESULTS: Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I. PPARgamma is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin. CONCLUSIONS: Curcumin can inhibit the proliferation and activation of HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2 and MMP-9. The effects of curcumin are mediated through activating the PPARgamma signal transduction pathway and associated with PPARgamma nuclear translocation/redistribution. SN - 0366-6999 UR - https://www.unboundmedicine.com/medline/citation/17531121/Effects_of_curcumin_on_peroxisome_proliferator_activated_receptor_gamma_expression_and_nuclear_translocation/redistribution_in_culture_activated_rat_hepatic_stellate_cells_ L2 - https://Insights.ovid.com/pubmed?pmid=17531121 DB - PRIME DP - Unbound Medicine ER -