Lipid microdomains (rafts) are cholesterol‐enriched dynamic ordered lipid domains belonging to cell membranes involved in diverse cellular functions, including signal transduction, membrane trafficking, and infection. Many studies have reported relationships between insulin signaling and lipid rafts. Likewise, links between insulin signaling and O ‐GlcNAcylation have also been described. However, the potential connection between O ‐GlcNAc and raft dynamics remains unexplored. Here we show that O ‐GlcNAc and the enzyme that creates this modification, O ‐GlcNAc transferase (OGT), are localized in rafts. On insulin stimulation, we observe time‐dependent increases in OGT expression and localization within rafts. We show that these processes depend on activation of the phosphatidylinositol 3‐kinase (PI3K) pathway. Inhibition of OGT does not significantly affect cholesterol synthesis and raft building but decreases insulin receptor expression and PI3K and mitogen‐activated protein kinase pathway activation. Taken together, these findings indicate that O ‐GlcNAcylation, lipid rafts, and signaling pathways are spatiotemporally coordinated to enable fundamental cellular functions.—Perez‐Cervera, Y., Dehennaut, V., Aquino Gil, M., Guedri, K., Solórzano Mata, C. J., Olivier‐Van Stichelen, S., Michalski, J.‐C., Foulquier, F., Lefebvre, T., Insulin signaling controls the expression of O ‐GlcNAc transferase and its interaction with lipid microdomains. FASEB J. 27, 3478–3486 (2013). www.fasebj.org

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of proteinO-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing proteinO-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of proteinO-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increasedO-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that proteinO-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed betweenO-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increasedO-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.

Background: Activation of the sympathetic nervous system attenuates inflammation via catecholamines. Recent evidence has shown that electroacupuncture (EA) activates neuronal networks involved in the release of dopamine and norepinephrine that control systemic inflammation. In muscle, catecholamines are related to cyclic adenosine monophosphate (cAMP). This signaling molecule has been implicated in recovery from sustained contractile activity, which may induce muscular pain, such as that which occurs during low back pain (LBP). Objective: Our aim was to evaluate the effects of EA used for the control of LBP on the activation of the sympathetic nervous system in a randomized controlled clinical trial in athletes. Methods: Two groups of athletes with acute or chronic low back pain were studied. EA, sham EA and pharmacological treatment (diclofenac sodium) were evaluated. The outcome measures included a pain score represented by a visual analogue scale (VAS) and serum levels of catecholamines quantified by enzyme-linked immunosorbent assay. In addition, blood was collected into chilled heparin tubes, placed in 96-well cell culture plates and incubated with an equal volume of Roswell Park Memorial Institute (RPMI) medium, with lipopolysaccharide (LPS) alone or with catecholamines. Tumor necrosis factor (TNF)-α levels in the supernatants were analyzed. Results: The results indicated that the initial pain ratings did not differ between the groups analyzed. EA induced epinephrine secretion but not norepinephrine or dopamine secretion. Although EA and pharmacological treatment did not differ in terms of pain relief, in vitro epinephrine and norepinephrine reduced TNF-α production in response to LPS stimuli. Conclusion: EA activates the sympathetic nervous system and induces the release of epinephrine, which could ameliorate inflammation and protect muscular tissue in addition to relieving pain.

Dental care to vulnerable population is a pending issue in health policies due to the lack of appropriate and specialized strategies. Children with sensory deficits represent a challenge to professionals in prevention of oral diseases fundamentally due to communication problems. This study was conducted to compare the simplified oral hygiene index (OHI-S) before and after a playful learning intervention in children with hearing impairment between 6 years and 11 years. Educational strategies were adopted for children with hearing impairment in Mexican Sign Language. The intervention consisted of three meetings explaining topics and activities of preventive content on health and oral hygiene for the children and their tutors. Simplified oral hygiene index was determinate before and after intervention. The mean of OHI-S score was 12% good status before the intervention and 64% after the application of the educational strategy. Teachers and dentists can enhance oral health promotion actions to children with hearing impairment in elementary institution using playful learning interventions. Ávila-Curiel BX, Solórzano-Mata CJ, Avendaño-Martínez JA, et al. Playful Educational Intervention for Improvement of Oral Health in Children with Hearing Impairment. Int J Clin Pediatr Dent 2019;12(6):491-493.

The Sd^a/Cad antigen reported on glycoconjugates of human tissues has an increasingly recognized wide impact on the physio‐pathology of different biological systems. The last step of its biosynthesis relies on the enzymatic activity of the β1,4‐N‐acetylgalactosaminyltransferase‐II (B4GALNT2), which shows the highest expression level in healthy colon. Previous studies reported the occurrence in human colonic cells of two B4GALNT2 protein isoforms that differ in the length of their cytoplasmic tail, the long isoform showing an extended 66‐amino acid tail. We examined here, the subcellular distribution of the two B4GALNT2 protein isoforms in stably transfected colonic LS174T cells and in transiently transfected HeLa cells using fluorescence microscopy. While a similar subcellular distribution at the trans‐Golgi cisternae level was observed for the two isoforms, our study pointed to an atypical subcellular localization of the long B4GALNT2 isoform into dynamic vesicles. We demonstrated a critical role of its extended cytoplasmic tail for its Golgi targeting and post‐Golgi sorting and highlighted the existence of a newly described post‐Golgi sorting signal as well as a previously undescribed fate of a Golgi glycosyltransferase.Database: The proteins β1,4GalNAcT II, β1,4‐GalT1, FucT I, FucT VI and ST3Gal IV are noted B4GALNT2, B4GALT1, FUT1, FUT6 and ST3GAL4, whereas the corresponding human genes are noted B4GALNT2, B4GALT1, FUT1, FUT6 and ST3GAL4 according to the HUGO nomenclature.