DOI: 10.1161/01.res.78.1.82. Hypoxia and Hypoxia/Reoxygenation Activate Raf-1, Mitogen-Activated Protein Kinase Kinase, Mitogen-Activated Protein Kinases, and S6 Kinase in Cultured Rat Cardiac Myocytes

Hypoxia and Hypoxia/Reoxygenation Activate Raf-1, Mitogen-Activated Protein Kinase Kinase, Mitogen-Activated Protein Kinases, and S6 Kinase in Cultured Rat Cardiac Myocytes

10.1161/01.res.78.1.82

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Abstract In response to hypoxia and reoxygenation, mammalian cells are known to express a variety of genes to adapt to these external stresses or lead to further cell damage. We investigated the intracellular signaling cascades in cultured rat cardiac myocytes subjected to hypoxia or hypoxia followed by reoxygenation (hypoxia/reoxygenation). Here, we show that both hypoxia and hypoxia/reoxygenation caused rapid activation of the mitogen-activated protein kinase kinase kinase (MAPKKK) activity of Raf-1. This was followed by the sequential activation of mitogen-activated protein kinase kinase (MAPKK), mitogen-activated protein (MAP) kinases, and S6 kinase (p90 rsk ). Furthermore, hypoxia caused hyperphosphorylation of Raf-1. The maximal hyperphosphorylation of Raf-1 appeared to be accompanied by a significant decrease in MAPKKK activity. These results strongly suggest the following: (1) Intracellular signals initiated by both hypoxia and hypoxia/reoxygenation converge on Raf-1 and activate its MAPKKK activity. Then, Raf-1 activates downstream serine/threonine kinases including MAPKK, MAP kinases, and p90 rsk . (2) Raf-1 is not only located upstream from MAPKK and MAP kinases but also may be phosphorylated by MAP kinases directly or indirectly, and at least Raf-1 kinase activity may be downregulated by this feedback mechanism.

Bibliography

Seko, Y., Tobe, K., Ueki, K., Kadowaki, T., & Yazaki, Y. (1996). Hypoxia and Hypoxia/Reoxygenation Activate Raf-1, Mitogen-Activated Protein Kinase Kinase, Mitogen-Activated Protein Kinases, and S6 Kinase in Cultured Rat Cardiac Myocytes. Circulation Research, 78(1), 82â90.

Authors 5

Yoshinori Seko (first)
Kazuyuki Tobe (additional)
Kohjiro Ueki (additional)
Takashi Kadowaki (additional)
Yoshio Yazaki (additional)

References 56 Referenced 96

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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:47 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 4:32 p.m.)
Indexed	2 days, 22 hours ago (Aug. 30, 2025, 1:18 p.m.)
Issued	29 years, 8 months ago (Jan. 1, 1996)
Published	29 years, 8 months ago (Jan. 1, 1996)
Published Print	29 years, 8 months ago (Jan. 1, 1996)

Funders 0

None

BibTeX

@article{Seko_1996, title={Hypoxia and Hypoxia/Reoxygenation Activate Raf-1, Mitogen-Activated Protein Kinase Kinase, Mitogen-Activated Protein Kinases, and S6 Kinase in Cultured Rat Cardiac Myocytes}, volume={78}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.78.1.82}, DOI={10.1161/01.res.78.1.82}, number={1}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Seko, Yoshinori and Tobe, Kazuyuki and Ueki, Kohjiro and Kadowaki, Takashi and Yazaki, Yoshio}, year={1996}, month=jan, pages={82–90} }

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