Protein synthesis inhibition induced by dimethylnitrosamine and diethylnitrosamine on isolated rat hepatocytes

The effect of microcystin-LR, an inhibitor of protein phosphatases PP1 and PP2A, was studied on protein synthesis by measuring the incorporation of labelled amino acid into protein in isolated rat hepatocytes. Microcystin-LR inhibited protein synthesis in the first minutes of the incubation period, and half-maximum effect was obtained at about 60 nM. Such an inhibition was also observed in the presence of different protein phosphatase inhibitors, i.e. okadaic acid, calyculin A and microcystin-RR. This effect was observed in whole hepatocytes, in the supernatant of the post-mitochondrial fraction and in the microsomal fraction. It was independent of a substrate supply and of the labelled amino acid used. Furthermore, this inhibition preceded the previously reported glucose-6-phosphatase activation induced by microcystin-LR [Claeyssens, Chédeville and Lavoinne (1993) FEBS Lett. 315, 7-10].

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Homocysteine enhances the inhibitory effect of extracellular adenosine on the synthesis of proteins in isolated rat hepatocytes

Biochemical Journal ◽

10.1042/bj3100893 ◽

1995 ◽

Vol 310 (3) ◽

pp. 893-896 ◽

Cited By ~ 12

Author(s):

S Tinton ◽

P Buc-Calderon

Keyword(s):

Protein Synthesis ◽

Kinase Inhibitor ◽

Adenine Nucleotides ◽

Rat Hepatocytes ◽

Isolated Hepatocytes ◽

Adenosine Kinase ◽

Isolated Rat Hepatocytes ◽

Extracellular Adenosine ◽

Inhibition Of Protein Synthesis ◽

Isolated Rat

Previous work has shown that extracellular adenosine inhibits the incorporation of radiolabelled leucine into proteins in isolated rat hepatocytes [Tinton, Lefebvre, Cousin and Buc Calderon (1993) Biochim. Biophys. Acta 1176, 1-6]. In this study, we investigated whether its metabolism into adenine nucleotides, inosine or S-adenosylhomocysteine (AdoHcy) is required to induce such an impairment. Incubation of isolated hepatocytes in the presence of adenosine at 0.5 or 1 mM reduces the synthesis of proteins by about 45% after 120 min of incubation. Such an inhibition occurred without cell lysis and was not modified by adding the adenosine kinase inhibitor 5-iodotubercidin (15 microM) or the adenosine deaminase inhibitor coformycin (0.1 microM). It is therefore unlikely that the anabolic and catabolic pathways of adenosine are involved in the inhibition of protein synthesis. Adenosine (1 mM) increased the level of AdoHcy and S-adenosylmethionine by 20- and 5-fold respectively after 60 min of incubation and reduced the methylation index. These events as well as the inhibition of protein synthesis were strongly enhanced in the presence of L-homocysteine (2 mM). It is therefore concluded that the metabolism of adenosine into AdoHcy, which is known to be a potent inhibitor of cellular methylation reactions, may play an important role in the control of translation.

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Effects of aminooxyacetate, alanine and other amino acids on protein synthesis in isolated rat hepatocytes

Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis ◽

10.1016/0005-2787(78)90148-x ◽

1978 ◽

Vol 520 (3) ◽

pp. 630-641 ◽

Cited By ~ 41

Author(s):

Per O. Seglen ◽

Anne E. Solheim

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Rat Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Isolated Rat

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Insulin stimulates synthesis of soluble proteins in isolated rat hepatocytes

Biochemical Journal ◽

10.1042/bj1900615 ◽

1980 ◽

Vol 190 (3) ◽

pp. 615-619 ◽

Cited By ~ 5

Author(s):

R L Clark ◽

R J Hansen

Keyword(s):

Protein Synthesis ◽

Rat Hepatocytes ◽

Isolated Hepatocytes ◽

Cellular Protein ◽

Soluble Proteins ◽

Leucine Incorporation ◽

Isolated Rat Hepatocytes ◽

Hepatic Protein Synthesis ◽

Isolated Rat ◽

Stimulation Of

The incorporation of [3H]leucine into soluble cellular protein was measured in isolated hepatocytes at extracellular leucine concentrations ranging from 0.15 to 20.0 mM. Insulin caused a 12—15% stimulation of [3H]leucine incorporation in the presence of high extracellular leucine concentrations. It is concluded that insulin causes a small but significant increase in the rate of hepatic protein synthesis.

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