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 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 (p90rsk). 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, Raf1 activates downstream serine/threonine kinases including MAPKK, MAP kinases and p90rsk. (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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Seko Y,Tobe K,Ueki K,Kadowaki T,Yazaki Ydoi
10.1161/01.res.78.1.82subject
Has Abstractpub_date
1996-01-01 00:00:00pages
82-90issue
1eissn
0009-7330issn
1524-4571journal_volume
78pub_type
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journal_title:Circulation research
pub_type: 杂志文章
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2012-02-03 00:00:00
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pub_type: 杂志文章
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更新日期:1987-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2003-03-21 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2001-12-07 00:00:00
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doi:10.1161/CIRCRESAHA.114.301374
更新日期:2014-01-17 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2002-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.2.179
更新日期:1997-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.1.57
更新日期:1983-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2016-06-24 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308645
更新日期:2016-08-19 00:00:00
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pub_type: 杂志文章
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更新日期:1991-03-01 00:00:00
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更新日期:2002-05-17 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2001-08-31 00:00:00
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pub_type: 杂志文章
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更新日期:1987-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-07-03 00:00:00
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pub_type: 杂志文章
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更新日期:1999-11-12 00:00:00
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更新日期:1996-05-01 00:00:00
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更新日期:1989-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1990-06-01 00:00:00
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更新日期:1976-12-01 00:00:00