AIM： To investigate the regulation of activin receptor-interacting protein 2 （ARIP2） expression and its possible relationships with collagen type Ⅳ （collagen Ⅳ） in mouse hepatoma cell line Hepal-6 cells. METHOD...AIM： To investigate the regulation of activin receptor-interacting protein 2 （ARIP2） expression and its possible relationships with collagen type Ⅳ （collagen Ⅳ） in mouse hepatoma cell line Hepal-6 cells. METHODS： The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation factors were analyzed by treatment with signal transduction activators such as phorbol 12-myristate 13-acetate （PMA）, forskolin and A23187. After pcDNA3- ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type Ⅱ receptor （ActRⅡ） and collagen Ⅳ expression were evaluated. RESULTS： The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation （2 or 4 h）. The ARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 （25.3% ± 5.7% vs 48.1% ± 3.6%, P 〈 0.01）. ARIP2 overexpression could remarkably suppress the expression of ActRⅡA mRNA in dose-dependent manner, but has no effect on ActRⅡB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen Ⅳ mRNA and protein expressions induced by activin A in Hapel-6 cells. CONCLUSION： These findings suggest that ARIP2 expression can be influenced by various factors. ARIP2 may participate in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA and play an important role in regulation of development of liver fibrosis induced by activin.展开更多
Naringin （1）, the highest-content flavanone glycoside in sour oranges, was incubated with human intestinal flora, and four biotransforrnation products （2-5） were obtained from the incubated mixture by chromatograp...Naringin （1）, the highest-content flavanone glycoside in sour oranges, was incubated with human intestinal flora, and four biotransforrnation products （2-5） were obtained from the incubated mixture by chromatographic methods. The chemical structures of the four products were elucidated as naringin-6＂acetate （2）, naringenin （3）, phloretic acid （4）, and phloroglucinol （5） on the basis of their spectroscopic data. Naringin-6＂-acetate was specifically formed by acetylation at C6-OH of glucosyl group of 1. The result obtained in the present research could account for the lower bioavailability of 1 after oral administration, suggesting that some biological properties of 1 in vivo may be mediated by its intestinal flora converted product 3. The biotransforrnation of 1 by intestinal flora leading to their systemic absorption deserves further attention and may provide valuable insights into pre-systemic drug metabolism, delivery or toxicity.展开更多
基金Supported by the National Natural Science Foundation of China, No. 30170478 and 30571688Science Projects of Jilin Province of China, No. 20060928-01
文摘AIM： To investigate the regulation of activin receptor-interacting protein 2 （ARIP2） expression and its possible relationships with collagen type Ⅳ （collagen Ⅳ） in mouse hepatoma cell line Hepal-6 cells. METHODS： The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation factors were analyzed by treatment with signal transduction activators such as phorbol 12-myristate 13-acetate （PMA）, forskolin and A23187. After pcDNA3- ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type Ⅱ receptor （ActRⅡ） and collagen Ⅳ expression were evaluated. RESULTS： The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation （2 or 4 h）. The ARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 （25.3% ± 5.7% vs 48.1% ± 3.6%, P 〈 0.01）. ARIP2 overexpression could remarkably suppress the expression of ActRⅡA mRNA in dose-dependent manner, but has no effect on ActRⅡB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen Ⅳ mRNA and protein expressions induced by activin A in Hapel-6 cells. CONCLUSION： These findings suggest that ARIP2 expression can be influenced by various factors. ARIP2 may participate in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA and play an important role in regulation of development of liver fibrosis induced by activin.
基金National Sciences and Technology Program of China (Grant No. 2011BAI07B08)"Major New Medicine Project" in Mega-projects of Science Research of China (Grant No. 2009ZX09301-010)
文摘Naringin （1）, the highest-content flavanone glycoside in sour oranges, was incubated with human intestinal flora, and four biotransforrnation products （2-5） were obtained from the incubated mixture by chromatographic methods. The chemical structures of the four products were elucidated as naringin-6＂acetate （2）, naringenin （3）, phloretic acid （4）, and phloroglucinol （5） on the basis of their spectroscopic data. Naringin-6＂-acetate was specifically formed by acetylation at C6-OH of glucosyl group of 1. The result obtained in the present research could account for the lower bioavailability of 1 after oral administration, suggesting that some biological properties of 1 in vivo may be mediated by its intestinal flora converted product 3. The biotransforrnation of 1 by intestinal flora leading to their systemic absorption deserves further attention and may provide valuable insights into pre-systemic drug metabolism, delivery or toxicity.
