β4GalT1 Mediates PPARγ N-Glycosylation to Attenuate Microglia Inflammatory Activation

Liu, Xiaojuan; Li, Aihong; Ju, Yuanyuan; Liu, Wangrui; Shi, Hui; Hu, Renyue; Zhou, Zijian; Sun, Xiaolei

doi:10.1007/s10753-018-0789-4

Cited by 6 publications

(4 citation statements)

References 68 publications

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“…11,16,17 Alterations of glycosylation of peroxisome proliferator-activated receptor c (PPARc) attenuate inflammatory activation of microglia. 18 Sialylation and fucosylation of N-linked and O-linked polysaccharides are altered in brain cancer, and these differences play critical roles in the progression of the cancer. 19 CSPGs are overexpressed in injured spinal cords and inhibit axonal regeneration.…”

Section: Introductionmentioning

confidence: 99%

Analysis of N- and O-Linked Glycosylation: Differential Glycosylation after Rat Spinal Cord Injury

Osimanjiang

Roballo

Houck

et al. 2020

Journal of Neurotrauma

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Glycosylation is a fundamental cellular process that has a dramatic impact on the functionality of glycoconjugates such as proteins or lipids and mediates many different biological interactions including cell migration, cellular signaling, and synaptic interactions in the nervous system. In spinal cord injury (SCI), all of these cellular processes are altered, but the potential contributions of glycosylation changes to these alterations has not been thoroughly investigated. We studied the glycosylation of injured spinal cord tissue from rats that received a contusion SCI. The N-and O-linked glycosylation was assessed at 3 and 14 days post-injury (DPI), and compared with uninjured control and time-matched sham spinal tissue. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and tandem MS (MS/MS) were performed to analyze carbohydrate structures. Results revealed diverse and abundant glycosylation in all groups, with some carbohydrate structures differentially produced in SCI animals compared with uninjured controls and shams. One such change occurred in the abundance of the Sda structure, Neu5Ac-a-(2,3)-[GalNAcb-(1,4)-]Gal-b-(1,4)-GlcNAc, which was increased in SCI samples compared with shams and non-injured controls. Immunohistochemistry (IHC) and western blot were performed on SCI and sham samples using the CT1 antibody, which recognizes the terminal trisaccharide of Sda with high specificity. Both of these metrics confirmed elevated Sda structure in SCI tissue, where IHC further showed that Sda is expressed mainly by microglia. The results of these studies suggest that SCI causes a significant alteration in N-and O-linked glycosylation.

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Section: Introductionmentioning

confidence: 99%

Analysis of N- and O-Linked Glycosylation: Differential Glycosylation after Rat Spinal Cord Injury

Osimanjiang

Roballo

Houck

et al. 2020

Journal of Neurotrauma

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“…One intriguing candidate protein is TNFR1, whereby α‐2,6 N ‐sialylation reportedly enhances pro‐inflammatory signaling on microglia [ 69 ]. Conversely, glycosylation of the microglia receptor CD200R is important for maintaining microglia in a homeostatic state upon interaction with neuronal CD200 [ 70 ] and N ‐glycosylation of peroxisome proliferator‐activated receptor γ suppresses microglia activation [ 71 ]. Several microglia‐associated N ‐glycoproteins are hyperglycosylated in AD, including Stabilin‐1, Intercellular Adhesion Molecule 1 (ICAM‐1), the NADPH oxidase (NOX2) component cytochrome b‐245, clusterin [ 20 ].Taken as a whole, our data supports an increase in N ‐sialylation may potentially modulate microglia functions within the plaque environment.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of plaque and microglia glycosylation in Alzheimer's disease

Fastenau,

Bunce,

Keating

et al. 2024

Brain Pathology

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Glycosylation is the most common form of post‐translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate‐associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O‐ and N‐linked glycans in autopsy‐confirmed AD post‐mortem brain tissue. Sialylated glycans facilitate important cellular functions including cell‐to‐cell interaction, cell migration, cell adhesion, immune regulation, and membrane excitability. Previous studies have not investigated both N‐ and O‐linked sialylated glycans in neurodegeneration. In this study, the location and distribution of sialylated glycans were evaluated in three brain regions (frontal cortex, hippocampus, and cerebellum) from 10 AD cases using quantitative digital pathology techniques. Notably, we found significantly greater N‐sialylation of the Aβ plaque microenvironment compared with O‐sialylation. Plaque‐associated microglia displayed the most intense N‐sialylation proximal to plaque pathology. Further analyses revealed distinct differences in the levels of N‐ and O‐sialylation between cored and diffuse Aβ plaque morphologies. Interestingly, phosphorylated tau pathology led to a slight increase in N‐sialylation and no influence of O‐sialylation in these AD brains. Confirming our previous observations in mice with novel histologic approach, these findings support microglia sialylation appears to have a relationship with AD protein aggregates while providing potential targets for therapeutic strategies.

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Section: Models Of Neuroinflammationmentioning

confidence: 99%

“…Liu et al showed that N-glycosylation of the peroxisome proliferator-activate receptor gamma (PPARγ) is crucial for the inflammatory activation of microglia [57]. Transfection of microglia with β-1,4-galactosyltransferase Ι (β4GalT1) attenuated the inflammatory activation of microglia through the N-glycosylation of PPARγ [57]. By contrast, Wang et al reported that β-1,4galactosyltransferase 5 (β4GalT5) is involved in the release of IL-1β from microglia stimulated by LPS [58] in vitro and in vivo.…”

Section: Models Of Neuroinflammationmentioning

confidence: 99%