Cell cycle proteins exhibit altered expression patterns in lentiviral-associated encephalitis.
Cell cycle proteins regulate processes as diverse as cell division and cell death. Recently their role in neuronal death has been reported in several models of neurodegeneration. We have reported previously that two key regulators of the cell cycle, the retinoblastoma susceptibility gene product (pRb) and transcription factor E2F1, exhibit altered immunostaining patterns in simian immunodeficiency virus encephalitis (SIVE). Here we show that E2F1 and the inactivated, hyperphosphorylated form of pRb (ppRb) also exhibit altered immunostaining patterns in human immunodeficiency virus encephalitis (HIVE). Quantification of E2F1 and ppRb staining by immunofluorescent confocal microscopy confirms a significant increase in E2F1 and ppRb in both HIVE and the simian model. This increase in E2F1 and ppRb staining correlates with an increase in the presence of activated macrophages, suggesting a link between changes in cell cycle proteins and the presence of activated macrophages. Changes in ppRb and E2F1 staining in SIVE also correlate with alterations in E2F/DNA binding complexes present in the nuclear and cytoplasmic fractions from both midfrontal cortex and basal ganglia. These findings suggest that changes in cell cycle proteins occur in both HIVE and the simian model and that these changes have functional implications for gene expression in neural cells under encephalitic conditions mediated by macrophage activation or infiltration.
Jordan-Sciutto
Kelly L
KL
Department of Pathology, Division of Neuropathology, , University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. jordan@path.dental.upenn.edu
Wang
Guoji
G
Murphey-Corb
Michael
M
Wiley
Clayton A
CA
D015526:AIDS Dementia Complex / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
D015415:Biomarkers; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D004247:DNA