Butyrate stimulates the secretion of apolipoprotein (apo) A-I and apo B100 by the human hepatoma cell line Hep G2. Induction of apo A-I mRNA with no change of apo B100 mRNA.
Addition of sodium butyrate to the culture medium of the human hepatoma cell line Hep G2 resulted in a time- and dose-dependent increase in the secretion of apolipoprotein A-I (apo A-I) and apolipoprotein B100 (apo B100). After a 24 h preincubation period, a 2.4- and 2.2-fold increase in the secretion of apo A-I and apo B100 respectively was obtained during the next 24 h in the presence of 2 mM-sodium butyrate. Secretion of albumin, fibrinogen or [35S]methionine-labelled newly synthesized proteins was unaffected or only marginally affected, indicating that the effect of butyrate on apo A-I and apo B100 is not part of a general effect on protein synthesis and secretion. In structure-function studies, butyrate was found to be the most potent inducer among various straight-chain carboxylic acids. Hydroxylated, aminated and otherwise modified butyrate derivatives were inactive. The enhanced accumulation of apo A-I and apo B100 in the culture medium could not be explained by changes in the uptake and degradation of the synthesized apolipoproteins or by alterations in the secretion of possible intracellular pools. In addition, [35S]methionine incorporation studies indicated that synthesis and/or secretion of newly synthesized apo A-I and apo B100 is enhanced in the presence of butyrate. The apo A-I mRNA level was increased 2.3-fold upon treatment with 2 mM-butyrate for 48 h, suggesting regulation at (post-)transcriptional level. In contrast, no change in the level of apo B100 mRNA in butyrate-treated cells was observed, indicating regulation at translational or co- or post-translational level. We propose that the effect of butyrate on the secretion of apo A-I and apo B100 by Hep G2 results from two different regulatory mechanisms.
Kaptein
A
A
Gaubius Institute TNO, Leiden, The Netherlands.
Roodenburg
L
L
Princen
H M
HM
D000418:Albumins / Q000378:metabolism; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000418:Albumins; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D002087:Butyrates; D012333:RNA, Messenger; D005340:Fibrinogen