Upregulation of phosphorylated alphaB-crystallin in the brain of children and young adults with Down syndrome.
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.
Palminiello
Sonia
S
Child Developmental Department, IRCCS San Raffaele Pisana, Rome and San Raffaele Cassino, Italy.
Jarząbek
Katarzyna
K
Child Developmental Department, IRCCS San Raffaele Pisana, Rome and San Raffaele Cassino, Italy.
Kaur
Kulbir
K
Child Developmental Department, IRCCS San Raffaele Pisana, Rome and San Raffaele Cassino, Italy.
Walus
Marius
M
New York State Institute for Basic Research in Developmental Disabilities, Department of Developmental Neurobiology, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Rabe
Ausma
A
New York State Institute for Basic Research in Developmental Disabilities, Department of Developmental Neurobiology, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Albertini
Giorgio
G
Child Developmental Department, IRCCS San Raffaele Pisana, Rome and San Raffaele Cassino, Italy.
Golabek
Adam A
AA
New York State Institute for Basic Research in Developmental Disabilities, Department of Developmental Neurobiology, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Kida
Elizabeth
E
New York State Institute for Basic Research in Developmental Disabilities, Department of Developmental Neurobiology, 1050 Forest Hill Road, Staten Island, NY 10314, USA. Electronic address: elizabethkida@gmail.com.
D000293:Adolescent; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000378:metabolism*; D004805:Ependyma / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D009836:Oligodendroglia / Q000378:metabolism; D010766:Phosphorylation; D010841:Pia Mater / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D038203:alpha-Crystallin B Chain; D012694:Serine; D020796:Receptor, Platelet-Derived Growth Factor alpha