In:
Science, American Association for the Advancement of Science (AAAS), Vol. 275, No. 5306 ( 1997-03-14), p. 1649-1652
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 (·O 2 − ). ·O 2 − 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 ·O 2 − through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably ·O 2 − , 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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.275.5306.1649
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
1997
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
