Effect of bacitracin on erythroid differentiation of MEL cells

Foresti, M.

doi:10.1007/bf00754466

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…The observation of binding of pyrophsophate and derivatives to Co(II)−Bc also implies that metallobacitracin may possibly bind several ubiquitous pyrophosphate-containing nucleotides, such as ADP, NAD + , FAD, and coenzyme A, to form complexes that can disturb energetic and metabolic regulations and influence a broader spectrum of homeostasis in the cells. In addition to its antibiotic activities, Bc also exhibits toxic effect toward nauplii and cysts of brine shrimp and affects erythroid differentiation . The oxidative activities and interactions with different biomolecules may be significant for the observed bioactivities of this metallopeptide.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its antibiotic activities, Bc also exhibits toxic effect toward nauplii and cysts of brine shrimp 57 and affects erythroid differentiation. 58 The oxidative activities and interactions with different biomolecules may be significant for the observed bioactivities of this metallopeptide. Future studies will further clarify this hypothesis and corroborate the important role of metal ions in the action of this metallopeptide.…”

Section: Discussionmentioning

confidence: 99%

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¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

et al. 2010

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The peptidyl antibiotic bacitracin (Bc) is one of the most widely used antibiotics which can bind divalent transition metal ions, including Mn(II), Co(II), Ni(II), Cu(II), and Zn(II). The metal binding is essential for its antimicrobial activity. Previous analysis of the hyperfine-shifted (1)H NMR signals of Co(II)-Bc A(1) revealed the structure of the metal binding environment and a potential hydrophobic site important for the bioactivity of this antibiotic. Co(II)-Bc in DMSO shows relatively sharper hyperfine-shifted (1)H NMR signals compared with the spectrum acquired in an aqueous solution, allowing more thorough analysis of the signals with 1D and 2D NMR methods. Pyrophosphate and derivatives bind to Co(II)-Bc to form kinetically inert ternary complexes. The coordinated D-Glu-4 is found detached from the metal center of metallobacitracin upon trimetaphosphate binding, implying its role in the antibiotic activity of Bc. We further demonstrate in this report the structure-function relationship on desamido-Bc of low antibiotic activity by the use of NMR, wherein D-Glu-4 is suggested to be important for the bioactivity of Bc. The interaction of the phospho-moiety with Bc is also reflected by DNA binding, wherein metal-free Bc does not bind DNA, whereas various metal complexes of Bc do. Cu(II)-Bc was further demonstrated to bind and oxidatively cleave DNA under reduction conditions in the air. It also exhibited a significant oxidative activity toward catechol oxidation, showing enzyme-like saturation kinetics with k(cat) = 7.0 x 10(-3) s(-1) and k(cat)/K(m) = 2.1 M(-1) s(-1) aerobically and k(cat) = 0.38 s(-1) and k(cat)/K(m) = 14.7 M(-1) s(-1) in the presence of 32 mM of H(2)O(2). The binding of pyrophosphate moiety to metallobacitracin, the detachment of d-Glu-4, and the significant oxidative activity of Cu(II)-Bc provide further insights into the bioactivity of this metallopeptide and Cu-oxygen chemistry.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

et al. 2010

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Toxicity of several important agricultural antibiotics to Artemia

et al. 1997

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A short low-level exposure to metavanadate during a cell cycle-specific interval of time is sufficient to permanently derange the differentiative properties of Mel cells

Foresti

Scippa²,

Mele³

et al. 2001

Mutagenesis

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Mouse erythroleukemia (Mel) cells have a cell cycle-dependent high sensitivity to chemical and physical mutagens. This report shows that a 5 h exposure to 0.1 or 0.01 microg/ml metavanadate during the initial period of erythroid differentiation induction was sufficient to permanently damage the ability of treated Mel cells and their progeny to undergo erythroid differentiation, without affecting cell viability and proliferation. Conversely, a 5 h pulse of metavanadate at 1 or 10 microg/ml inhibited both differentiation and cell proliferation. The cell cycle-dependent period of mutagenesis was essential for fixation of damage in the cell genome and the progeny of the cells treated with 0.1 or 0.01 microg/ml metavanadate stably inherited an impaired capacity to differentiate. The efficiency of the DNA repair synthesis machinery during the specific period of exposure of Mel cells seemed directly involved in damage fixation. In fact, the mutagenic effects of a 0.1 microg/ml metavanadate pulse was further increased in the presence of 1 mM hydroxyurea, an inhibitor of DNA repair synthesis. In contrast, 5 microg/ml vanillin, an antimutagenic agent that stimulates repair, completely restored the capacity of progeny of cells treated with 0.1 microg/ml metavanadate to complete differentiation. Determination of [(3)H]deoxythymidine in acid-insoluble DNA indicated that incorporation was stimulated by metavanadate alone and was further increased by metavanadate plus vanillin; conversely, incorporation of thymidine was reduced in the presence of hydroxyurea. The capacity of metavanadate to permanently damage Mel cell erythroid differentiation appeared to depend on the cell cycle-related efficiency of the DNA repair systems, activated to correct the induced alteration, rather than on a specific concentration.

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Effect of bacitracin on erythroid differentiation of MEL cells

Cited by 3 publications

References 12 publications

¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

Toxicity of several important agricultural antibiotics to Artemia

A short low-level exposure to metavanadate during a cell cycle-specific interval of time is sufficient to permanently derange the differentiative properties of Mel cells

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Effect of bacitracin on erythroid differentiation of MEL cells

Cited by 3 publications

References 12 publications

1H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

1H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

Toxicity of several important agricultural antibiotics to Artemia

A short low-level exposure to metavanadate during a cell cycle-specific interval of time is sufficient to permanently derange the differentiative properties of Mel cells

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¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity

¹H NMR, Mechanism, and Mononuclear Oxidative Activity of the Antibiotic Metallopeptide Bacitracin: The Role of d-Glu-4, Interaction with Pyrophosphate Moiety, DNA Binding and Cleavage, and Bioactivity