title: Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.
abstract: We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Sada
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.|Department of Molecular Diabetology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kukidome
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshinaga
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kajihara
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sonoda
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.|Department of Molecular Diabetology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senokuchi
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002417:Cattle; D015687:Cell Hypoxia; D002460:Cell Line; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D005353:Fibronectins; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D005947:Glucose