ROLE OF O-GLCNACYLATION ON THE ABNORMAL VASCULAR FUNCTION IN RATS FED WITH A HIGH FAT DIET

• Grant number: 12/04880-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2012
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Victor Vitorino Lima
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

O-Linked attachment of ²-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic post-translational modification that plays a key role in signal transduction pathways. The cycling of O-GlcNAc on proteins is controlled by two highly conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation is a post-translational modification that alters the function of numerous proteins important in vascular function, including kinases, phosphatases, transcription factors, and cytoskeletal proteins. Recent evidence from our laboratory suggests that augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli. Vascular resistance in large arteries appears to be greater in the cerebral circulation than in other vascular beds. Large arteries such as the basilar artery importantly contribute to total cerebral vascular resistance and are also major determinants of local microvascular pressure. In addition, stroke-associated injury is directly linked to the vascular structure and function where the stroke takes place. Considering that (1) the diet may influence stroke risk via several mechanisms, (2) a high fat diet augments O-GlcNAc levels, (3) augmented O-GlcNAc interferes with vascular responses, and (4) the effects of increased O-GlcNAcylation in cerebral arteries as well as how a high fat diet changes O-GlcNAc levels in cerebral vessels have not been addressed, the aim of the present study is to investigate whether changes in O-GlcNAcylation modifies vascular reactivity in the rat basilar artery and if a high fat diet interferes with the O-GlcNAc pathway in cerebral vessels. We hypothesized that a high fat diet increases O-GlcNAc levels in cerebral arteries, which in turn leads to increased vascular contractile responses.