Hypergravity induces expression of cyclooxygenase-2 in the heart vessels

Abstract

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.

COX-2-dependent and potentially cardioprotective effects of negative inotropic substances released after ischemia

“…COX-2 is not constitutively expressed in cardiomyocytes but is rather induced by various stress factors, e.g., cytokines, mechanical stress factors, or phenomena, that occur during ischemiareperfusion (1,21,(31)(32)(33). COX-2 is basally expressed in the cardiomyocytes used in our experiments.…”

“…COX-2 is inducibly expressed in cells (1,33). We therefore performed Western blot analysis to investigate whether COX-2 is expressed in isolated cardiomyocytes laminated and stained with fura-2 AM.…”

“…COX-1 is constitutively expressed, whereas COX-2 is inducible as an immediate early gene by various stress factors. Expression of COX-2 is intensified after cell damage (22,33,45) as well as after ischemia (1,38).…”

Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway

“…Two principal isoforms of COX, COX-1 and COX-2, have been identified. COX-1 is constitutively expressed in various normal tissues and exerts a variety of physiological functions, whereas COX-2 is rapidly induced in response to a number of stimuli, including growth factors and cytokines (Smith et al, 2000;Gupta and Dubois, 2001;Ricci et al, 2003;Oshima et al, 2005). Since many cancer tissues, including colorectal cancer tissues, produce various growth factors and cytokines (Bates et al, 1990;Salomon et al, 1995;Yarden and Sliwkowski, 2001;Tamura et al, 2002;Li et al, 2004;Montano and Djamgoz, 2004), COX-2 derived from advanced colorectal cancer cells seems to be induced by various growth factors and cytokines within the tumors (Bates et al, 1990;Eberhart et al, 1994;Salomon et al, 1995;Gupta and Dubois, 2001;Yarden and Sliwkowski, 2001;Tamura et al, 2002;Ricci et al, 2003;Li et al, 2004;Montano and Djamgoz, 2004).…”

Increased Level of Serum Vascular Endothelial Growth Factor by Long-Term Exposure to Hypergravity

“…Since opportunities for conducting animal experiments under microgravity are limited, experiments under hypergravity are important using special centrifugation apparatus (see below). The results from such hypergravity experiments We have previously demonstrated that short-term exposure to hypergravity at 2G for 4 h [2G (4H)] induces expression of cyclooxygenase-2 (COX-2; gene symbol, Ptgs2) in the heart [7]. COX-2 is a rate-limiting enzyme for prostaglandin biosynthesis, which plays important roles in a variety of pathological responses including tumorigenesis and diabetes [5,6,8].…”