Premium
Signalling the molecular stress response to nephrotoxic and mutagenic cysteine conjugates: Differential roles for protein synthesis and calcium in the induction of c‐fos and c‐myc mRNA in LLC‐PK1 cells
Author(s) -
Yu Kefu,
Chen Qin,
Liu Hong,
Zhan Yi,
Stevens James L.
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041610215
Subject(s) - signalling , cysteine , messenger rna , chemistry , differential (mechanical device) , calcium signaling , calcium , conjugate , nephrotoxicity , microbiology and biotechnology , biochemistry , biology , signal transduction , gene , genetics , kidney , enzyme , mathematical analysis , mathematics , organic chemistry , aerospace engineering , engineering
Nephrotoxic and mutagenic cysteine conjugates (NCC) are activated by the enzyme cysteine conjugate, β‐lyase, to reactive acylating species which bind covalently to cellular macromolecules. We now show that an early event after treatment of LLC‐PK1 cells with NCC is the induction of mRNA for both c‐fos and c‐myc . Treatment with S‐(1,2‐dichlorovinyl)‐L‐cysteine (DCVC) induced c‐fos (53‐fold) and c‐myc mRNA (20‐fold) and increased transcription about 3‐fold for both genes. Covalent binding was required for induction of both mRNAs. Dithiothreitol partially prevented induction of both c‐fos and c‐myc RNA. Buffering the DCVC‐induced increase in cytosolic free calcium had no effect on c‐fos mRNA but partially blocked c‐myc mRNA induction. Cycloheximide blocked the induction of c‐myc mRNA in the absence of an effect on c‐fos induction. The data suggest that the increase in c‐fos mRNA is a primary response to DCVC toxicity and occurs without a requirement for protein synthesis or an increase in intracellular free calcium. In contrast, c‐myc induction requires protein synthesis, suggesting that the presence of another primary response factor may regulate induction either transcriptionally or posttranscriptionally. The data suggest that different signalling pathways regulate induction of c‐fos and c‐myc mRNA in response to stress caused by reactive acylating species. © 1994 Wiley‐Liss, Inc.