Differential effects of chloramphenicol and its nitrosoanalogue on protein synthesis and oxidative phosphorylation in rat liver mitochondria

Samir Abou-Khalil, Wafa H. Abou-Khalil, Adel A. Yunis

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Abstract

Protein synthesis and oxidative phosphorylation were chosen as measures to study the differences between the effects of chloramphenicol (CAP) and its derivative nitroso-chloramphenicol (NO-CAP) on rat liver mitochondria. [14C]Leucine incorporation into mitochondrial protein was inhibited 83 per cent by 30 μM CAP and was equally inhibited by a similar concentration of thiamphenicol; 30μM NO-CAP, however, inhibited [14C]leucine incorporation only 34 per cent and 30μM nitrosobenzene had no effect. A millimolar concentration of CAP was required to inhibit oxidative phosphorylation, whereas 75 μM NO-CAP was inhibitory. Unlike CAP, NO-CAP at 100 μM slightly inhibited state 4 respiration with glutamate as substrate, but slightly activated it with succinate. Respiratory state 3 with glutamate was completely inhibited by 75 μM NO-CAP, whereas the same concentration of CAP was only 10 per cent inhibitory. With succinate, 250 μM NO-CAP was required to inhibit state 3, whereas 600 μM CAP had no effect. The uncoupled state triggered by 2,4-dinitrophenol in the presence of either glutamate or succinate was inhibited totally by NO-CAP, but not by CAP. The inhibition by NO-CAP was mitochondrial protein dependent, for more NO-CAP was required for inhibition with a larger amount of protein. NO-CAP effects could be prevented or released by cysteine, but not by washing. Oxidative phosphorylation was also inhibited by another nitroso compound, nitrosobenzene, which, however, did not affect mitochondrial protein synthesis. The results indicate that, unlike CAP, NO-CAP is a potent inhibitor of the energy conserving mechanism.

Original languageEnglish (US)
Pages (from-to)2605-2609
Number of pages5
JournalBiochemical Pharmacology
Volume29
Issue number19
DOIs
StatePublished - Jan 1 1980

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Keywords

  • CAP, chloramphenicol
  • DNP, 2,4-dinitrophenol
  • M, mitochondria
  • NO-Benz, nitrosobenzene
  • NO-CAP, nitroso-chloramphenicol
  • PABA, p-aminobenzoic acid
  • TAP. thiamphenicol

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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