Upregulation of phosphorylated alphaB-crystallin in the brain of children and young adults with Down syndrome
| Autor: | Adam A. Golabek, Marius Walus, Elizabeth Kida, Kulbir Kaur, Katarzyna Jarząbek, Ausma Rabe, Giorgio Albertini, Sonia Palminiello |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Pathology Down syndrome Receptor Platelet-Derived Growth Factor alpha Adolescent Central nervous system Biology Lesion White matter Young Adult Downregulation and upregulation Crystallin Heat shock protein Internal medicine Ependyma Glial Fibrillary Acidic Protein medicine Serine Humans Phosphorylation Child Molecular Biology General Neuroscience Brain Infant alpha-Crystallin B Chain medicine.disease Up-Regulation Oligodendroglia Endocrinology medicine.anatomical_structure Astrocytes Child Preschool Pia Mater Neurology (clinical) medicine.symptom Down Syndrome Chromosome 21 Developmental Biology |
| Zdroj: | Brain research. 1268 |
| ISSN: | 1872-6240 |
| Popis: | Our previous proteomic studies disclosed upregulation of alphaB-crystallin, a small heat shock protein, in the brain tissue of Ts65Dn mice, a mouse model for Down syndrome (DS). To validate data obtained in model animals, we studied at present the levels and distribution of total alphaB-crystallin and its forms phosphorylated at Ser-45 and Ser-59 in the brain tissues of DS subjects and age-matched controls at 4 months to 23 years of age. On immunoblots from frontal cortex and white matter, alphaB-crystallin and its form phosphorylated at Ser-59 were detectable already in infants, whereas alphaB-crystallin phosphorylated at Ser-45 appeared in small amounts in older children. Although the levels of total alphaB-crystallin were modestly increased in DS subjects, the amounts of both phosphorylated forms were much higher (up to approximately 550%) in the group of older children and young adults with DS than in age-matched controls. Immunoreactivity to alphaB-crystallin occurred not only in a subset of oligodendrocytes and some subpial and perivascular astrocytes, which was reported earlier, but also in GFAP-positive astrocytes accumulating at the sites of ependymal injury as well as some GFAP/platelet-derived growth factor receptor alpha-positive cells in both DS and control brains, which is a novel observation. Given that the chaperone and anti-apoptotic activities of alphaB-crystallin are phosphorylation-dependent, we propose that enhanced phosphorylation of alphaB-crystallin in the brains of young DS subjects might reflect a cytoprotective mechanism mobilized in response to stress conditions induced or augmented by the effect of genes encoded by the triplicated chromosome 21. |
| Databáze: | OpenAIRE |
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