| | |  | | | | Record from Web of Science® | | | | | | |
| Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts |
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| Author(s): Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, GoldschmidtClermont PJ |
| Source: SCIENCE Volume: 275 Issue: 5306 Pages: 1649-1652 Published: MAR 14 1997 |
| Times Cited: 828 References: 48 |
| 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21205 USA
2. UNIV N CAROLINA, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA
3. UNIV MICHIGAN, MED CTR, ANN ARBOR, MI 48109 USA
4. NHLBI, CARDIOL BRANCH, NIH, BETHESDA, MD 20892 USA
5. JOHNS HOPKINS UNIV, SCH MED, DEPT CELL BIOL & ANAT, BALTIMORE, MD 21205 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: WN123 |
| ISSN: 0036-8075 |
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