Autoregulation of actin synthesis in hepatocytes by transcriptional and posttranscriptional mechanisms.
Treatment of rat hepatocytes with the filamentous-actin-stabilizing toxin phalloidin decreased the amount of globular actin by 77% in the cytosol and by 80% in the nucleus within 12 h. Simultaneously, actin mRNA was specifically increased by 230%. The de-novo synthesis of actin mRNA, as measured by nuclear run-on transcription, was enhanced by 250%. Treatment of cells with actinomycin D blocked the increase of actin mRNA. The apparent half-life of actin mRNA was not significantly altered during treatment with phalloidin. In contrast, the globular-actin-stabilizing botulinum C2 toxin increased the amount of cytosolic globular actin by 50% within 12 h. Simultaneously, the actin mRNA level was decreased by 62%. However, de-novo synthesis of actin mRNA was not impaired. The apparent half-life of actin mRNA was decreased by approximately 60% during treatment with C2 toxin. The data strongly suggest an autoregulatory control of actin synthesis on the basis of the globular/filamentous actin ratio in rat hepatocytes at the transcriptional as well as at the posttranscriptional levels.
Reuner
K H
KH
Institut für Klinische Chemie und Pathobiochemie, Universität Giessen, Germany.
Wiederhold
M
M
Dunker
P
P
Just
I
I
Bohle
R M
RM
Kröger
M
M
Katz
N
N
D000199:Actins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D006706:Homeostasis; D008099:Liver / Q000378:metabolism*; D010590:Phalloidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D000199:Actins; D012333:RNA, Messenger; D010590:Phalloidine; D001905:Botulinum Toxins