Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts

K IRANI; Y XIA; J. L ZWEIER; S. J SOLLOTT; C. J DER; E. R FEARON; M SUNDARESAN; T FINKEL; P. J GOLDSCHMIDT-CLERMONT

doi:10.1126/science.275.5306.1649

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Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts

Journal article

Peer reviewed

Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts

K IRANI, Y XIA, J. L ZWEIER, S. J SOLLOTT, C. J DER, E. R FEARON, M SUNDARESAN, T FINKEL and P. J GOLDSCHMIDT-CLERMONT

Science (American Association for the Advancement of Science), Vol.275(5306), pp.1649-1652

1997

DOI: 10.1126/science.275.5306.1649

PMID: 9054359

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Abstract

NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21Ras, H-RasV12 (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-RasV12 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-RasV12-transformed cells. Thus, H-RasV12-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.

Cell Physiology

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Molecular and cellular biology

Cell cycle, cell proliferation

Details

Title: Subtitle: Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts
Creators: K IRANI - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
Y XIA - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
J. L ZWEIER - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
S. J SOLLOTT - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
C. J DER - Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
E. R FEARON - University of Michigan Medical Center, Ann Arbor, MI 48109, United States
M SUNDARESAN - Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States
T FINKEL - Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States
P. J GOLDSCHMIDT-CLERMONT - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.275(5306), pp.1649-1652
Publisher: American Association for the Advancement of Science; Washington, DC
DOI: 10.1126/science.275.5306.1649
PMID: 9054359
ISSN: 0036-8075
eISSN: 1095-9203
Language: English
Date published: 1997
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047664202771

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