PMID- 11112425 OWN - NLM STAT- MEDLINE DCOM- 20010118 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 279 IP - 1 DP - 2000 Dec 9 TI - Regulation of HGF/SF gene expression in MRC-5 cells by N-acetylcysteine. PG - 108-15 AB - The effect of N-acetylcysteine (NAC) on levels of hepatocyte growth factor/scatter factor (HGF/SF) gene transcripts was investigated in the human lung embryonic fibroblast cell line, MRC-5. NAC increased expression of HGF/SF mRNA, in a dose- and time-dependent fashion, by a mechanism independent of glutathione synthesis but sensitive to oxidant stress induced by H(2)O(2). Using actinomycin D to block RNA synthesis, it was observed that NAC had no effect on the stability of the HGF/SF mRNA transcripts. NAC increased HGF/SF promoter activity in cells transiently transfected with chloramphenicol acetyltransferase (CAT) reporter genes driven by HGF/SF gene 5'-flanking sequences. Primer extension analysis demonstrated that NAC enhanced the expression of HGF/SF mRNA transcribed from the main transcription initiation site. Although the 5' flanking region of the HGF/SF gene contains a sequence at -1019 to -1011 with homology to the NF-kappaB response element, electrophoretic mobility shift assay demonstrated that this site did not bind nuclear factors in MRC-5 cells in the presence or absence of NAC. In contrast to the effect on HGF/SF mRNA, NAC did not increase HGF/SF protein production by MRC-5 cells. CI - Copyright 2000 Academic Press. FAU - Harrison, P M AU - Harrison PM AD - Institute of Liver Studies, GKT School of Medicine, King's Denmark Hill Campus, Bessemer Road, London, SE5 9PJ, United Kingdom. phillip.harrison@kcl.ac.uk FAU - Farzaneh, F AU - Farzaneh F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (DNA Primers) RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Animals MH - Base Sequence MH - Cell Line MH - Chloramphenicol O-Acetyltransferase/genetics MH - DNA Primers MH - Electrophoresis/methods MH - Gene Expression Regulation/*drug effects MH - Hepatocyte Growth Factor/*genetics MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics EDAT- 2000/12/09 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/12/09 11:00 PHST- 2000/12/09 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/09 11:00 [entrez] AID - S0006-291X(00)93904-4 [pii] AID - 10.1006/bbrc.2000.3904 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2000 Dec 9;279(1):108-15. doi: 10.1006/bbrc.2000.3904.