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Regulation of D-ß-Hydroxybutyrate Dehydrogenase in Rat Hepatoma Cell Lines¹

Department of Biology, University of Alabama, Tuscaloosa, Alabama 35487-0344

Quantitation of D-ß-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 10⁵ cpm/min/10⁶ cells). The H4-II-EC3 cell line grew more slowly (48.5-h doubling time) and had lower protein biosynthesis rate (1.46 x 10⁵ cpm/min/10⁶ cells). The protein synthesis rate in hepatocytes was 1.25 x 10⁵ cpm/min/10⁶ 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.

¹ This work is supported by National Cancer Institute Grant CA-21103 to R. Lindahl and University of Alabama Research Grant Committee Grant to P. Churchill.

² To be submitted to the Graduate School of the University of Alabama in partial fulfillment of the requirements for PhD degree in Biology.

³ To whom requests for reprints should be addressed, at Department of Biology, Box 870344, University of Alabama, Tuscaloosa, AL 354870344.

Received 9/13/88. Revised 12/13/88. Accepted 1/16/89.

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