Hypergravity induces expression of cyclooxygenase-2 in the heart vessels.
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)-1alpha 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-1alpha induction.
Oshima
Masanobu
M
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Oshima
Hiroko
H
Taketo
Makoto M
MM
D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018471:Hypergravity; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases