Induction of liver apolipoprotein A-IV mRNA in porphyric mice.

We have isolated cDNA clones for mRNAs that are induced by porphyria from a mouse liver library. Of the three inducible clones isolated, we have identified one as being apolipoprotein A-IV (apo A-IV) by its extensive homology with a rat apolipoprotein A-IV cDNA sequence. The level of liver apo A-IV mRNA increases rapidly in response to either of two porphyrogenic drugs. When the ferrochelatase-inhibited drug, 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) is used, a 6 and 28 fold induction of liver apo A-IV mRNA is observed in male and female mice, respectively. If the heme-destroying porphyrogenic drug, allylisopropylacetamide (AIA) is the inducing agent, liver apo A-IV mRNA levels increase 2-3 fold in both males and females. The level of apo A-IV mRNA reaches a maximum within 6-10 hr. after drug administration. Intestine apo A-IV mRNA levels do not change during either of these drug-induced porphyrias. RNA from acute-phase responsive liver or liver from mice treated with bilirubin, porphobilinogen, or protoporphyrin IX show no increase in apo A-IV mRNA. These results indicate that apo A-IV induction is tied to a disruption in porphyrin-heme biosynthesis but is not directly affected by several heme intermediates nor by the major heme degradation product, bilirubin.