Factors regulating alphal (I) collagen mRNA turnover

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To know a short-term effect of the intragastric administration of 50% carbon tetrachloride to the rat at a dosage of 2 ml/kg, hepatic mRNA turnover was examined during the initial three days. Northern analysis demonstrated that type I collagen alphal chain mRNA which was trace in the normal liver increased to about 30 times higher level 72h after the CCl_4 administration. The extent of the increase was much higher than those reported previously. By comparison with the normal rat, the degradation rate of this mRNA did not appear to be altered, and instead the gene for this protein was estimated to be three times more actively transcried.Unlike this mRNA,Northern analysis also demonstrated that serum albumin mRNA is reduced at the initial stage within a time course examined. Serum albumin mRNA which was turned over with a half-life of 60h in the normal liver decayd with a half-life of 4h until about 6h after the CCl_4 administration. At this initial stage, the albumin gene transcription was simultaneously lowered below 10% of the normal activity, and this suppressed condition was prolonged over 48h. Because of the two reasons, in liver, mRNA for albumin first decreased. The rapid degradation of this mRNA,however, reached the apparent cessation, followed by the phase at which there is no more degradation of albumin mRNA,consequently giving its level half as much as that in the normal rat liver for following 48h. While rranscription activation of the type I collagen alphal chain gene was shown to be responsible for the increase in its mRNA level, both the transcription suppression and the stimulation in mRNA degradation were causative of the marked reduction of albumin mRNA.Glyceraldehyde-3-phosphate dehydrogenase mRNA level appeared to be stationary throughout the couse examined. The results demonstrate that the toxic condition induced in liver of the rat exposed to orally administered CCl_4 affects turnover of different mRNA species through different mechanisms.