Suppression of cytochrome P-450 expression by epidermal growth factor(EGF) in primary culture of mouse hepatocytes = 일차 배양 간세포에서 Epidermal Growth Factor(EGF) 에 의한 Cytochrome P-450 발현 억제

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The suppressive effect of epidermal growth factor(EGF) on drug-metabolizing activity was investigated in primary culture of mouse hepatocytes. EGF decreaed P-450IA-specific ethoxyresorufin O-deethylase(EROD) activity, P-450IIB-specific penthoxyresorufin O-dialkylase(PROD) activity, and P-450IIIA-specific erythromycin N-demethylase(ERDM) activity significantly. EGF(0.1-10 $\mu$g/ml) reduced EROD activity in dose and time-dependentmanner during 3 day cultures. At the lowest concentration, 0.1 $\mu$g/ml, EGF could decrease EROD activity meaningfully. The suppressive effect of EGF appeared at 4 hr, and reached maximum within 24 hr. PROD activity was also inhibited bited by EGF in 3 day cultures, but at relatively high concentration of EGF (10$\mu$g/ml). In contrast to EROD, PROD activity showed weak dose-dependency of EGF treatment. Dephosphorylation experiments showed that the inhibition of EROD and PROD activity was not resulted from phosphorylation of microsomal roteins. ERDM activity was also subject to EGF. In the case of PROD and ERDM, EGF reduced the basal activtity of enzymes as well as chemical(2mM phenobarbital and 10 $\mu$M dexamethasone, respectively)-induced activity, while the basal EROD activity was elevated slightly by EGF in 3 day cultures. Western immunoblot analysis with P-450IA- and P-450IIB-specific monoclonal antibodies showed that the inhibition of phenotypic enzyme activities was found to be due to the decrease of amount of proteins. This change of protein amount was resulted from reduction of mRNA expression by EGF, which was proved in RNA slot blot analysis.
Advisors
Yang, Kyu-Hwan양규환
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
1993
Identifier
68314/325007 / 000911428
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 1993.2, [ v, 50 p. ]

URI
http://hdl.handle.net/10203/28402
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=68314&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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