TY - JOUR
T1 - AHR, a novel acute hypoxia-response sequence, drives reporter gene expression under hypoxia in vitro and in vivo
AU - Cilek, Mehmet Zeynel
AU - Hirohata, Satoshi
AU - Hatipoglu, Omer Faruk
AU - Ogawa, Hiroko
AU - Miyoshi, Toru
AU - Inagaki, Junko
AU - Ohtsuki, Takashi
AU - Harada, Hiroshi
AU - Kamikawa, Shigeshi
AU - Kusachi, Shozo
AU - Ninomiya, Yoshifumi
PY - 2011/1
Y1 - 2011/1
N2 - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an early immediate gene. We have previously reported that ADAMTS1 was strongly induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter-driven reporter signal is detectable by acute hypoxia. We constructed the GFP (green fluorescent protein) expression vector [AHR (acute hypoxia-response sequence)-GFP] under the control of ADAMTS1 promoter and compared it with the constitutive GFP-expressing vector under the control of CMV (cytomegalovirus promoter-GFP). We transduced AHR-GFP and examined whether GFP signals can be detected under the acute hypoxia. When the human umbilical vein [HUVEC (human umbilical vein endothelial cells)] was transduced under normoxia, there were few GFP signals, while CMVGFP showed considerable GFP signals. When HUVEC was stimulated with hypoxia, GFP signals from AHR-GFP gene were induced under hypoxic conditions. Notably, the GFP signals peaked at 3 h under hypoxia. In ischaemic hind limb model, transduced AHR-GFP showed hypoxic induction of GFP signals. In summary, we have demonstrated that the AHR system induced the reporter gene expression by acute hypoxia, and its induction is transient. This is the first report showing the unique acute hypoxia-activated gene expression system.
AB - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an early immediate gene. We have previously reported that ADAMTS1 was strongly induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter-driven reporter signal is detectable by acute hypoxia. We constructed the GFP (green fluorescent protein) expression vector [AHR (acute hypoxia-response sequence)-GFP] under the control of ADAMTS1 promoter and compared it with the constitutive GFP-expressing vector under the control of CMV (cytomegalovirus promoter-GFP). We transduced AHR-GFP and examined whether GFP signals can be detected under the acute hypoxia. When the human umbilical vein [HUVEC (human umbilical vein endothelial cells)] was transduced under normoxia, there were few GFP signals, while CMVGFP showed considerable GFP signals. When HUVEC was stimulated with hypoxia, GFP signals from AHR-GFP gene were induced under hypoxic conditions. Notably, the GFP signals peaked at 3 h under hypoxia. In ischaemic hind limb model, transduced AHR-GFP showed hypoxic induction of GFP signals. In summary, we have demonstrated that the AHR system induced the reporter gene expression by acute hypoxia, and its induction is transient. This is the first report showing the unique acute hypoxia-activated gene expression system.
KW - A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)
KW - Hypoxia
KW - Metalloproteinase
KW - Promoter
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U2 - 10.1042/CBI20100290
DO - 10.1042/CBI20100290
M3 - Article
C2 - 20795945
AN - SCOPUS:78649685749
VL - 35
SP - 1
EP - 8
JO - Cell Biology International Reports
JF - Cell Biology International Reports
SN - 1065-6995
IS - 1
ER -