Eisuke Kawakubo1, Takuya Matsumoto2,3, Keiji Yoshiya1, Sho Yamashita1, Tomoko Jogo1, Hiroshi Saeki1, Eiji Oki1, Tadashi Furuyama1, Yoshinao Oda4, Yoshihiko Maehara2. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan maehara@surg2.med.kyushu-u.ac.jp tak@iuhw.ac.jp. 3. Department of Medicine, International University of Health and Welfare, Narita, Japan. 4. Department of Anatomic Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND/AIM: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and human gastric cancer tissues. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNA-transfected HUVECs. Additionally, guanosine 3',5' cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficient mice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in human gastric cancer tissues. RESULTS: BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNA-transfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. CONCLUSION: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation. Copyright
BACKGROUND/AIM: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and humangastric cancer tissues. MATERIALS AND METHODS:Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNA-transfected HUVECs. Additionally, guanosine 3',5' cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficientmice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in humangastric cancer tissues. RESULTS:BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNA-transfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Humangastric cancer tissues with low BUBR1 expression showed no eNOS expression. CONCLUSION: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation. Copyright