Myelin disruptions are frequently reported in human immunodeficiency virus (HIV)-infected individuals and can occur in the CNS very early in the disease process. Immature oligodendrocytes (OLs) are quite sensitive to toxic increases in [Ca2+ ]i caused by exposure to HIV-1 Tat (transactivator of transcription, a protein essential for HIV replication and gene expression), but sensitivity to Tat-induced [Ca2+ ]i is reduced in mature OLs. Tat exposure also increased the activity of Ca2+ /calmodulin-dependent kinase IIβ (CaMKIIβ), the major isoform of CaMKII expressed by OLs, in both immature and mature OLs. Since CaMKIIβ is reported to interact with glycogen synthase kinase 3β (GSK3β), and GSK3β activity is implicated in OL apoptosis as well as HIV neuropathology, we hypothesized that disparate effects of Tat on OL viability with maturity might be because of an altered balance of CaMKIIβ-GSK3β activities. Tat expression in vivo led to increased CaMKIIβ and GSK3β activity in multiple brain regions in transgenic mice. In vitro, immature murine OLs expressed higher levels of GSK3β, but much lower levels of CaMKIIβ, than did mature OLs. Exogenous Tat up-regulated GSK3β activity in immature, but not mature, OLs. Tat-induced death of immature OLs was rescued by the GSK3β inhibitors valproic acid or SB415286, supporting involvement of GSK3β signaling. Pharmacologically inhibiting CaMKIIβ increased GSK3β activity in Tat-treated OLs, and genetically knocking down CaMKIIβ promoted death in mature OL cultures treated with Tat. Together, these results suggest that the effects of Tat on OL viability are dependent on CaMKIIβ-GSK3β interactions, and that increasing CaMKIIβ activity is a potential approach for limiting OL/myelin injury with HIV infection.
Pubmed ID: 30674062 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsThis unknown targets CaMKII beta/gamma
View all literature mentionsThis polyclonal targets CAMK2B
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsImage analysis software that acquires, analyzes, and archives research data without altering raw findings. It integrates data and changes how pixels are mapped to the screen for clearer display, rather than altering the pixels of the image data itself.
View all literature mentionsThermo Fisher Scientific. Catalog number. P36934. ProLong™ Gold Antifade Mountant. Cellular Imaging
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsDigital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsMus musculus with name C57BL/6N-Camk2btm1a(EUCOMM)Hmgu/Cnrm from IMSR.
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis unknown targets CaMKII beta/gamma
View all literature mentionsImage analysis software that acquires, analyzes, and archives research data without altering raw findings. It integrates data and changes how pixels are mapped to the screen for clearer display, rather than altering the pixels of the image data itself.
View all literature mentionsThis monoclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
View all literature mentions