Oxygen governs Galβ1–3GalNAc epitope in human placenta

Abstract

It is becoming increasingly apparent that the dynamics of glycans reflect the physiological state of cells involved in several cell functions including growth, response to signal molecules, migration, as well as adhesion to, interaction with, and recognition of other cells. The presence of glycoconjugates in human placenta suggests their major role in maternal-fetal exchanges, intercellular adhesion, cellular metabolism, and villous vessel branching. Although several studies have described glycoconjugate distribution in the human placenta descriptions of their physiological function and control mechanisms during placental development are lacking. In this study we investigated the developmental distribution and regulation of placental core 1 O- and N-glycans focusing on early and late first trimester human pregnancy. To define the control mechanisms of the oligosaccharide chains during early placentation process, chorionic villous explants and human trophoblast cell lines were exposed to various oxygen levels. We found that oxygen tension regulates changes in core-1 O-glycan (the disaccharide Galβ1-3GalNAc) epitope expression levels. Moreover, by double affinity chromatography and subsequent analysis with mass spectrometry, we identified in the heat shock protein 90-α (HSP90α) a good candidate as carrier of the Galβ1-3GalNAc epitope at low oxygen tension. Our results support a fundamental role of oxygen tension in modulating glycosylation of proteins during placental development.

Localized Chemical Remodeling for Live Cell Imaging of Protein‐Specific Glycoform

“…As a control and as expected, no band appears on the antibiotin membrane for the pristine MCF‐7 cells (Figure B). To further demonstrate protein site specificity, six glycoproteins, including three glycoproteins bearing experimentally confirmed terminal Gal/GalNAc (transferrin receptor,– Hsp90 α,,, annexin II,,) (Supporting Information, Figure S8) and three regularly encountered glycoproteins (integrin α5, ENO1,, Hsp27) (Supporting Information, Figure S9), are purified with immunoprecipitation, and none of these glycoproteins are modified under LCM condition. As an additional control, MCF‐7 cells undergoing direct treatment with GO identifies multiple bands on the antibiotin membrane (Supporting Information, Figure S10), suggesting the occurrence of non‐selective modification.…”

Golgi pH, Ion and Redox Homeostasis: How Much Do They Really Matter?

“…Reactive oxygen species and hypoxia (low oxygen environment) are key modulators of the cellular redox state (Adler et al, 1999). ROS and hypoxia also modulate Golgi-associated vesicular trafficking, protein sorting and glycosylation events (Regoeczi et al, 1991; Koike et al, 2004; Yin et al, 2006; Shirato et al, 2011; Ermini et al, 2013; Lehnus et al, 2013; Belo et al, 2015). Most often, this is thought to be mediated mainly by hypoxia-inducible factors (HIF-1-3) that regulate the expression of hundreds of genes, including a variety of proteins involved in glycosylation.…”

Hypoxia and Reactive Oxygen Species as Modulators of Endoplasmic Reticulum and Golgi Homeostasis

“…In addition to protein folding, hypoxia and ROS affect many other cellular pathways including transcription, translation, vesicular trafficking, pH homeostasis, energy metabolism, autophagy, proliferation and cell death, as well as tumor cell invasion and metastasis (11,27,139). Several recent studies have also shown that ROS and hypoxia not only impair Golgi-associated vesicular trafficking and protein sorting steps, but also alter glycosylation (10,40,186). Therefore, the Golgi is by no means different from any other organelle known to be affected by ROS and hypoxia.…”