Regulation of D-beta-hydroxybutyrate dehydrogenase in rat hepatoma cell lines.

Abstract

Quantitation of D-beta-hydroxybutyrate dehydrogenase (BDH) in normal rat hepatocytes was compared with that in two rat hepatoma cell lines, H4-II-EC3 and RLT-3C. BDH activity in normal rat hepatocyte mitochondria was 321 nmol/min/mg, which was greatly reduced to 10.7 nmol/min/mg and 1.7 nmol/min/mg in H4-II-EC3 and RLT-3C cell mitochondria, respectively. The cell growth rate and L-[35S]methionine incorporation rate showed that RLT-3C cells had the highest growth rate (32.4-h doubling time) and the fastest protein biosynthesis rate (2.65 x 10(5) cpm/min/10(6) cells). The H4-II-EC3 cell line grew more slowly (48.5-h doubling time) and had lower protein biosynthesis rate (1.46 x 10(5) cpm/min/10(6) cells). The protein synthesis rate in hepatocytes was 1.25 x 10(5) cpm/min/10(6) cells. These results suggest that there is a reciprocal correlation between BDH activity and cell growth and protein synthesis rates. Immunochemical quantitation of BDH showed the amount of BDH in H4-II-EC3 and RLT-3C cells was about 4.8 and 0.5% of that in normal rat hepatocytes, respectively. Quantitation of BDH by biosynthesis indicated that BDH content in H4-II-EC3 cells and RLT-3C cells was 9.3 and 4.0% of that of normal hepatocytes, respectively. Precursor BDH synthesized by in vitro translation primed with RNA of H4-II-EC3 cells or RLT-3C cells was 3.0 and 1.1% of that translated from normal rat hepatocyte RNA. These results suggest that the decrease in BDH content in hepatoma cells results from a decrease in functional BDH-mRNA. The coupling of a decrease in BDH activity with an increase in activity of succinyl-CoA: acetoacetyl-CoA transferase in hepatoma cells may play a role in generating additional energy required for the rapid growth of tumor cells.

• Authors: W W Zhang, S Churchill, R Lindahl, P Churchill
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 9 Pg. 2433-7 (May 01 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2706630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• RNA, Messenger
• Hydroxybutyrate Dehydrogenase
• Coenzyme A-Transferases

Topics

• Animals
• Cell Division
• Coenzyme A-Transferases (analysis)
• Hydroxybutyrate Dehydrogenase (analysis, biosynthesis, genetics)
• Liver Neoplasms, Experimental (enzymology, pathology)
• Mitochondria, Liver (enzymology)
• Neoplasm Proteins (biosynthesis)
• Protein Biosynthesis
• RNA, Messenger (analysis)
• Rats
• Rats, Inbred Strains
• Tumor Cells, Cultured