Aflatoxin B1: effect on the synthesis and degradation of mitochondrial proteins in hepatocyte monolayers.
The effect of aflatoxin B1 (AFB1), a hepatocarcinogen, on mitochondrial and general protein synthesis and degradation has been studied. AFB1 (0.003, 0.03, 0.25 micrograms ml-1) inhibited total protein synthesis over a 5 h period by 30, 64 and 82%, respectively, measured by incorporation of [3H]leucine. After 24 h in the presence of AFB1 inhibition was 23, 77 and 100%, respectively. AFB1 inhibited total hepatocyte protein degradation in a concentration independent manner by approximately 50% i.e., from 1.4% h-1 to 0.7% h-1. The immediate effect of AFB1 on mitoribosomal and total mitochondrial protein synthesis and mitochondrial degradation has been assessed by two methods. Mitoribosomal synthesis of proteins was inhibited over a 5 h period by AFB1 in a concentration independent manner by approximately 43%. Total mitochondrial protein synthesis showed a 23 and 45% inhibition by AFB1 (0.003 and 0.03 micrograms AFB1 ml-1) over a 4 h period and 25 and 72% inhibition, respectively, after 24 h in culture. The rate of mitochondrial protein degradation was not altered. AFB1 inhibits dibutyryl cyclic AMP-induced tyrosine amino transferase (TAT) activity in hepatocytes by 57% at 0.003 micrograms ml-1 and 100% at 0.03 micrograms ml-1 over a 24 h period. Dibutyryl cyclic AMP increases the rate of degradation of proteins in hepatocyte monolayers from 1.4% h-1 to 2.7% h-1 and was inhibited at both concentrations of AFB1 used. AFB1 causes a rapid inhibition of total hepatocyte protein synthesis, synthesis of proteins in hepatocyte mitochondria and the synthesis of imported mitochondrial proteins. General hepatocyte and dibutyryl cyclic AMP-induced protein degradation are significantly inhibited by AFB1 whereas the degradation of mitochondrial proteins is unaffected.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004790:Enzyme Induction; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D000348:Aflatoxins; D002273:Carcinogens; D011506:Proteins; D016604:Aflatoxin B1; D014444:Tyrosine Transaminase