• O-GlcNAcylation and oxidation of proteins: is signalling in the cardiovascular system becoming sweeter?

      Lima, Victor V.; Spitler, Kathryn M.; Choi, Hyehun; Webb, R. Clinton; Tostes, Rita C.; Department of Physiology (2012-10-1)
      O-GlcNAcylation is an unusual form of protein glycosylation, where a single-sugar [GlcNAc (N-acetylglucosamine)] is added (via β-attachment) to the hydroxyl moiety of serine and threonine residues of nuclear and cytoplasmic proteins. A complex and extensive interplay exists between O-GlcNAcylation and phosphorylation. Many phosphorylation sites are also known glycosylation sites, and this reciprocal occupancy may produce different activities or alter the stability in a target protein. The interplay between these two post-translational modifications is not always reciprocal, as some proteins can be concomitantly phosphorylated and O-GlcNAcylated, and the adjacent phosphorylation or O-GlcNAcylation can regulate the addition of either moiety. Increased cardiovascular production of ROS (reactive oxygen species), termed oxidative stress, has been consistently reported in various chronic diseases and in conditions where O-GlcNAcylation has been implicated as a contributing mechanism for the associated organ injury/protection (for example, diabetes, Alzheimer's disease, arterial hypertension, aging and ischaemia). In the present review, we will briefly comment on general aspects of O-GlcNAcylation and provide an overview of what has been reported for this post-translational modification in the cardiovascular system. We will then specifically address whether signalling molecules involved in redox signalling can be modified by O-GlcNAc (O-linked GlcNAc) and will discuss the critical interplay between O-GlcNAcylation and ROS generation. Experimental evidence indicates that the interactions between O-GlcNAcylation and oxidation of proteins are important not only for cell regulation in physiological conditions, but also under pathological states where the interplay may become dysfunctional and thereby exacerbate cellular injury.
    • The Role of Uridine Adenosine Tetraphosphate in the Vascular System

      Matsumoto, Takayuki; Tostes, Rita C.; Webb, R. Clinton; Department of Physiology (2011-11-1)
      The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up4A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up4A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up4A modulates vascular function by actions on endothelial and smooth muscle cells. In this paper, we discuss the effects of Up4A on vascular function and a potential role for Up4A in cardiovascular diseases.