Protection by selective amino acid solutions against doxorubicin induced growth inhibition of Escherichia coli.

Abstract

1. Incubation of Escherichia coli with 0.7 mM doxorubicin in MBS-glucose medium resulted in complete growth inhibition, an inhibition that was blocked by placing specific amino acids (AA) in the medium. 2. The mechanism of protection by AA was similar to that reported previously for cells poisoned by hyperoxia and by paraquat, e.g. of 20 common AA, ten percent, ten do not and the branched-chair AA are among those required for inhibition. 3. Unlike hyperoxia and paraquot stringency which caused elevation of intracellular concentrations of guanosine tetraphosphate (ppGpp), doxorubicin inhibition did not elevate ppGpp. 4. Concentrations of ppGpp were increased by isoleucine starvation as expected, and the subsequent addition of doxorubicin did not abolish that increase; however, pretreatment with doxorubicin prevented the induction of stringency by isoleucine starvation. 5. This suggests that doxorubicin directly inhibits ppGpp synthesis or protein biosynthesis to leave tRNA loaded as is the case with chloramphenicol.

• Authors: H S Amash, O R Brown, V A Padron
• Journal: General pharmacology (Gen Pharmacol) Vol. 26 Issue 5 Pg. 983-7 (Sep 1995) ISSN: 0306-3623 [Print] England
• PMID: 7557272 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amino Acids
• Antibiotics, Antineoplastic
• Bacterial Proteins
• Culture Media
• Nucleotides
• Guanosine Tetraphosphate
• Doxorubicin
• Paraquat

Topics

• Amino Acids (biosynthesis, pharmacology)
• Antibiotics, Antineoplastic (antagonists & inhibitors, pharmacology)
• Bacterial Proteins (biosynthesis)
• Culture Media
• Doxorubicin (antagonists & inhibitors, pharmacology)
• Escherichia coli (drug effects, growth & development, metabolism)
• Guanosine Tetraphosphate (biosynthesis)
• Nucleotides (metabolism)
• Oxidative Stress (physiology)
• Paraquat (pharmacology)