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Molecular mechanism of antimutagenicity by an ethoxy-substituted phylloquinone (vitamin K1 derivative) from spinach (Spinacea oleracea L.).
Kumar, Sanjeev; Tripathi, Jyoti; Srivastava, Ashish K; Gautam, Satyendra.
Afiliación
  • Kumar S; Food Technology Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.
  • Tripathi J; Food Technology Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.
  • Srivastava AK; Nuclear Agriculture and Biotechnology Division, Mumbai, 400 085, India; Homi Bhabha National Institute, Mumbai, 400 094, India.
  • Gautam S; Food Technology Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India; Homi Bhabha National Institute, Mumbai, 400 094, India. Electronic address: sgautam@barc.gov.in.
Chem Biol Interact ; 330: 109216, 2020 Oct 01.
Article en En | MEDLINE | ID: mdl-32810488
In our previous study, an antimutagenic compound from spinach (Spinacea oleracea L.), ethoxy-substituted phylloquinone (ESP) was isolated and characterized. The current study deals with elucidation of the possible mechanism of antimutagenicity of ESP against ethyl methanesulfonate (EMS) deploying model systems such as human lymphoblast (TK+/- or TK6) cell line (thymidine kinase gene mutation assay) and Escherichia coli MG1655 (rifampicin resistance assay). Findings of the study ruled out the possibility of direct inactivation of EMS by ESP. DAPI competitive binding assay indicated the DNA minor groove binding activity of ESP. Interestingly, ESP did not display major groove binding or intercalating abilities. Further, proteomics study using 2-D gel electrophoresis in E. coli and subsequent studies involving single gene knockout strains revealed the possible role of tnaA (tryptophanase) and dgcP (diguanylate cyclase) genes in observed antimutagenicity. These genes have been reported to be involved in indole and cyclic-di-GMP biosynthesis, respectively, which eventually lead to cell division inhibition. In case of TK+/- cell line system, ADCY genes (adenylate cyclase), a functional analogue of dgcP gene, were found to be transcriptionally up-regulated. The generation/doubling time were significantly higher in E. coli or TK+/- cells treated with ESP than control cells. The findings indicated inhibition of cell proliferation by ESP through gene regulation as a possible mechanism of antimutagenicity across the biological system. Cell division inhibition actually provides additional time for the repair of damaged DNA leading to antimutagenicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina K 1 / Mutagénesis / Spinacia oleracea Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Chem Biol Interact Año: 2020 Tipo del documento: Article País de afiliación: India Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina K 1 / Mutagénesis / Spinacia oleracea Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Chem Biol Interact Año: 2020 Tipo del documento: Article País de afiliación: India Pais de publicación: Irlanda