title: Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats.
abstract: Changes in the levels of O-linked N-acetyl-glucosamine (O-GlcNAc) on nucleocytoplasmic protein have been associated with a number of age-related diseases such as Alzheimer's and diabetes; however, there is relatively little information regarding the impact of age on tissue O-GlcNAc levels. Therefore, the goal of this study was to determine whether senescence was associated with alterations in O-GlcNAc in heart, aorta, brain and skeletal muscle and if so whether there were also changes in the expression of enzymes critical in regulating O-GlcNAc levels, namely, O-GlcNAc transferase (OGT), O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase (GFAT). Tissues were harvested from 5- and 24-month old Brown-Norway rats; UDP-GlcNAc, a precursor of O-GlcNAc was assessed by HPLC, O-GlcNAc and OGT levels were assessed by immunoblot analysis and GFAT1/2, OGT, O-GlcNAcase mRNA levels were determined by RT-PCR. In the 24-month old animals serum insulin and triglyceride levels were significantly increased compared to the 5-month old group; however, glucose levels were unchanged. Protein O-GlcNAc levels were significantly increased with age (30-107%) in all tissues examined; however, paradoxically the expression of OGT, which catalyzes O-GlcNAc formation, was decreased by approximately 30% in the heart, aorta and brain. In the heart increased O-GlcNAc was associated with increased UDP-GlcNAc levels and elevated GFAT mRNA while in other tissues we found no difference in UDP-GlcNAc or GFAT mRNA levels. These results demonstrate that senescence is associated with increased O-GlcNAc levels in multiple tissues and support the notion that dysregulation of pathways leading to O-GlcNAc formation may play an important role in the development of age-related diseases.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Fülöp
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Cell Biology, MCLM 684, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: László G
authors.initials: LG
authors.lastname: Nőt
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Charlye A
authors.initials: CA
authors.lastname: Brocks
authors.affiliation: Department of Cell Biology, MCLM 684, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Marchase
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Miller
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, USA. jchatham@uab.edu.|Department of Cell Biology, MCLM 684, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. jchatham@uab.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Chatham
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D011506:Proteins; D012333:RNA, Messenger; D000117:Acetylglucosamine