Biomaterial Database

Induction of metallothionein gene expression by epidermal growth factor and its inhibition by transforming growth factor-beta and dexamethasone in rat hepatocytes. 1995

P Moffatt, and G L Plaa, and F Denizeau

Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.

Metallothionein (MT) is a small cysteine-rich protein thought to be mainly involved in metal regulation and detoxification. The implication of MT in cell growth and differentiation has also been suggested. This latter hypothesis was further investigated in adult rat hepatocytes induced to proliferate by epidermal growth factor (EGF). Exposure of hepatocytes to EGF resulted in significant increases (approximately twofold) in MT protein and MT-1 messenger RNA (mRNA) levels, which were maximal after 48 hours. As revealed by nuclear run-on analysis, these changes were the result of transcriptional activation. Increases of MT occurred concomitantly with stimulation of DNA synthesis (48 hours). Addition of ZnSO4 or dexamethasone (Dex) was also effective at inducing MT protein (approximately 3.6 to 3.3 times) and mRNA. Combined addition of Zn and EGF produced an additive increase in MT protein and MT-1 mRNA levels. When both Dex and EGF were present together, the EGF-induced MT protein and mRNA expression was lost, whereas it had only minor inhibitory effects on DNA synthesis. Transforming growth factor beta (TGF-beta), a known antagonist of EGF on hepatocytes, blocked the EGF-induced MT accumulation and stimulation of DNA synthesis. In addition, under the same conditions, the EGF-induced c-fos mRNA accumulation was blocked by Dex whereas TGF-beta had no effect. These results show that growth factors believed to play a role in liver regeneration can also modulate MT gene expression in vitro. This modulation does not strictly parallel that of DNA synthesis. The possibility that c-fos stimulation may play a role in MT induction by EGF cannot be ruled out.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008668	Metallothionein	A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.	Isometallothionein,Metallothionein A,Metallothionein B,Metallothionein I,Metallothionein II,Metallothionein IIA
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated