AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticci...AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P＜0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.展开更多
Objective: To study the relationship between signal regulatory protein az (SIRPα1) and hep-atocellular carcinoma (HCC) and explore the possible molecular mechanisms. Methods: Total RNA was extracted from normal hepat...Objective: To study the relationship between signal regulatory protein az (SIRPα1) and hep-atocellular carcinoma (HCC) and explore the possible molecular mechanisms. Methods: Total RNA was extracted from normal hepatocyte cell line Hs680, Hepatocellular carcinoma cell lines HepG2, H4-H7,Chang liver and SK-Hepl. The SIRPα1 expression was determined by Northern blot. The mRNA and protein expression of SIRPα1 was detected in 42 pathologically confirmed hepatocellular carcinoma tissue samples and 6 normal liver tissues by Northern blot and immunohistochemical staining. The association of SIRPα1 and HGF was determined in HUH7. Results: SIRPα1 was highly expressed in Hs680, HepG2 and H4-H7, but weakly expressed in SK-Hepl and Chang liver cell lines. Northern blot and Western blot both detected the reduced expression of SIRPα1 in hepatocellular carcinoma tissue as compare to paracancerous and normal tissues. In vitro experiments showed HGF stimulation elevated SIRPα1 phosphorylation. Over-expression of wild type SIRPα1 promoted cell proliferation in the presence of HGF. Conclusion: SIRPα1 might be involved in HCC development and metastasis. The underlying mechanisms may be related to regulatory tyrosine phosphorylation of SIRPα1 by HGF stimulation.展开更多
基金Military Medical Science Found of China,No.98Q050
文摘AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P＜0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.
文摘Objective: To study the relationship between signal regulatory protein az (SIRPα1) and hep-atocellular carcinoma (HCC) and explore the possible molecular mechanisms. Methods: Total RNA was extracted from normal hepatocyte cell line Hs680, Hepatocellular carcinoma cell lines HepG2, H4-H7,Chang liver and SK-Hepl. The SIRPα1 expression was determined by Northern blot. The mRNA and protein expression of SIRPα1 was detected in 42 pathologically confirmed hepatocellular carcinoma tissue samples and 6 normal liver tissues by Northern blot and immunohistochemical staining. The association of SIRPα1 and HGF was determined in HUH7. Results: SIRPα1 was highly expressed in Hs680, HepG2 and H4-H7, but weakly expressed in SK-Hepl and Chang liver cell lines. Northern blot and Western blot both detected the reduced expression of SIRPα1 in hepatocellular carcinoma tissue as compare to paracancerous and normal tissues. In vitro experiments showed HGF stimulation elevated SIRPα1 phosphorylation. Over-expression of wild type SIRPα1 promoted cell proliferation in the presence of HGF. Conclusion: SIRPα1 might be involved in HCC development and metastasis. The underlying mechanisms may be related to regulatory tyrosine phosphorylation of SIRPα1 by HGF stimulation.
