Hypergravity induces expression of cyclooxygenase-2 in the heart vessels
Hypergravity induces expression of cyclooxygenase-2 in the heart vessels
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DOI：
10.1016/j.bbrc.2005.03.060
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发表时间：
2005-05-13
影响因子：
3.1
通讯作者：
Taketo, MM
中科院分区：
文献类型：
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作者：
Oshima, M;Oshima, H;Taketo, MM
环氧合酶-2（考克斯-2）是前列腺素生物合成的限速酶，在包括机械应力在内的各种刺激下被诱导，并在病理生理条件下起重要作用。例如，已显示重力应力诱导骨组织中考克斯-2的表达，这对于骨稳态是必需的。为了研究考克斯-2是否是由重力负荷在骨以外的其他组织中诱导的，我们将小鼠暴露于2G和3G的超重力4小时。我们在这里证明，考克斯-2诱导小鼠心脏血管的超重力。此外，缺氧诱导因子（HIF）-1 α及其下游基因，如诱导型一氧化氮合酶，血管内皮生长因子，血红素加氧酶-1在心脏中同时诱导，而这些基因在考克斯-2（-/-）小鼠心脏中没有诱导。因此，在心脏中诱导的考克斯-2通过诱导HIF-1 α来帮助保护心脏功能免受超重条件下的缺氧。(c)2005年爱思唯尔公司All rights reserved.
Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin biosynthesis, is induced by various stimuli including mechanical stress and plays important roles in pathophysiological conditions. For example, gravitational stress has been shown to induce expression of COX-2 in bone tissues, which is essential for bone homeostasis. To investigate whether COX-2 is induced by gravitational loading in other tissues than bone, we exposed mice to hypergravity at 2G and 3G for 4 h. We demonstrate here that COX-2 is induced in the mouse heart vessels by hypergravity. Moreover, hypoxia-inducible factor (HIF)-1 alpha and its downstream genes such as inducible nitric oxide synthase, vascular endothelial growth factor, and heme oxygenase-1 were induced in the heart simultaneously, while none of these genes were induced in the COX-2(-/-) mouse heart. Therefore, COX-2 induced in the heart helps protect the heart function against hypoxia under hypergravity condition through HIF-1 alpha induction. (c) 2005 Elsevier Inc. All rights reserved.