Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts

Kaikobad Irani, Yong Xia, Jay L. Zweier, Steven J. Sollott, Channing J. Der, Eric R. Fearon, Maitrayee Sundaresan, Toren Finkel, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

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Abstract

NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21(Ras), H-Ras(V12) (v-H-Ras or EJ-Ras), produced large amounts of the reactive oxygen species superoxide (·O2-). ·O2- production was suppressed by the expression of dominant negative isoforms of Ras or Rac1, as well as by treatment with a farnesyltransferase inhibitor or with diphenylene iodonium, a flavoprotein inhibitor. The mitogenic activity of cells expressing H-Ras(V12) was inhibited by treatment with the chemical antioxidant N-acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK) activity was decreased and c-Jun N-terminal kinase (JNK) was not activated in H-Ras(V12)-transformed cells. Thus, H-Ras(V12)-induced transformation can lead to the production of ·O2- through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably ·O2-, as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation.

Original languageEnglish
Pages (from-to)1649-1652
Number of pages4
JournalScience
Volume275
Issue number5306
DOIs
StatePublished - Mar 14 1997
Externally publishedYes

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Flavoproteins
Mitogen-Activated Protein Kinases
Oxidants
Reactive Oxygen Species
Protein Isoforms
Fibroblasts
Antioxidants
Proto-Oncogene Proteins p21(ras)
Farnesyltranstransferase
JNK Mitogen-Activated Protein Kinases
Acetylcysteine
Superoxides
Cell Cycle
Phosphotransferases
diphenyleneiodonium
protein kinase N

ASJC Scopus subject areas

  • General

Cite this

Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., ... Goldschmidt-Clermont, P. (1997). Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science, 275(5306), 1649-1652. https://doi.org/10.1126/science.275.5306.1649

Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. / Irani, Kaikobad; Xia, Yong; Zweier, Jay L.; Sollott, Steven J.; Der, Channing J.; Fearon, Eric R.; Sundaresan, Maitrayee; Finkel, Toren; Goldschmidt-Clermont, Pascal.

In: Science, Vol. 275, No. 5306, 14.03.1997, p. 1649-1652.

Research output: Contribution to journalArticle

Irani, K, Xia, Y, Zweier, JL, Sollott, SJ, Der, CJ, Fearon, ER, Sundaresan, M, Finkel, T & Goldschmidt-Clermont, P 1997, 'Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts', Science, vol. 275, no. 5306, pp. 1649-1652. https://doi.org/10.1126/science.275.5306.1649
Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER et al. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science. 1997 Mar 14;275(5306):1649-1652. https://doi.org/10.1126/science.275.5306.1649
Irani, Kaikobad ; Xia, Yong ; Zweier, Jay L. ; Sollott, Steven J. ; Der, Channing J. ; Fearon, Eric R. ; Sundaresan, Maitrayee ; Finkel, Toren ; Goldschmidt-Clermont, Pascal. / Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. In: Science. 1997 ; Vol. 275, No. 5306. pp. 1649-1652.
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