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Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species

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Abstract

An underinvestigated aspect of the mitogenic and cell regulatory actions of vanadium is the regulation of gene expression. Among the fifteen cellular genes studied in cultured mouse C127 cells, vanadium (as 10 μM sodium vanadate) increased levels of mRNA of the actin and c-Ha-ras to four times control values. These increases represented de novo synthesis of mRNA, since they were inhibited by actinomycin D. Vanadate did not increase mRNA corresponding to c-src, c-mos, c-myc, p53, HSP70, pODC or RB genes, and expression of c-erb A, c-erb B, c-sis and c-fes genes was undetectable whether vanadium was present or not. Expression of a third gene affected by vanadium, c-jun, was augmented by addition of a reductant or oxidant together with the vanadate. Addition of NADH (marginally effective on its own) or H2O2 (effective alone) dramatically enhanced the effect of vanadate on c-jun gene expression. Catalase inhibited the effect of NADH partly. The vanadate-stimulated expression of actin and c-Ha-ras mRNA were unaffected by oxidants, reductants, metal chelators, or anti-oxidant enzymes. Evidently vanadate acts by two separate mechanisms on these two categories of genes. The alternate hypothesis that the actions of vanadate on actin and c-Ha-ras were mediated by a protein kinase cascade was inconsistent with the following observations. Neither insulin nor epidermal growth factor increased mRNA levels of c-Ha-ras or actin gene. Neither genistein (a tyrosine kinase inhibitor) nor pretreatment with 12-O-tetradecanoylphorbol-13-acetate blocked the actions of vanadate on these genes. Clearly the biological actions of vanadium depend in part on altered expression of genes. Since two of the genes are proto-oncogenes, this mechanism is potentially relevant to the mitogenic responses of cells to vanadium.

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Abbreviations

TPA:

(12-O-tetradecanoylphorbol-13-acetate)

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Authors and Affiliations

  1. Bioenergetics Research Laboratory, Faculty of Applied Sciences, Simon Fraser University, V5A 1S6, Burnaby, British Columbia, Canada

    Xuefeng Yin & Allan J. Davison

  2. British Columbia Cancer Research Centre, Environmental Carcinogenesis Section, Division of Epidemiology, Biometry and Occupational Oncology, 601 West 10th Avenue, V5Z 1L3, Vancouver, BC, Canada

    Xuefeng Yin, Allan J. Davison & Siu Sing Tsang

  3. Department of Medical Genetics, University of British Columbia, V6T 1W5, Vancouver, BC, Canada

    Siu Sing Tsang

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  1. Xuefeng Yin
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Yin, X., Davison, A.J. & Tsang, S.S. Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. Mol Cell Biochem 115, 85–96 (1992). https://doi.org/10.1007/BF00229100

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  • DOI: https://doi.org/10.1007/BF00229100

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