Function of alphaB-crystallin in brain development and neurodegeneration

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It has been shown by immunohistochemical studies that alphaB-crystallin accumulated in the reactive and neoplastic glial cells in a variety of pathologic situations. We investigated the phenotypic effects of selectively altering the levels of alphaB-crystallin in cultured glial cells by genetic manipulation. Glioma cells were transfected with a rat alphaB-crystallin sense cDNA or an antisense cDNA to alter cellular levels of alphaB-crystallin. The anti-sense strategy resulted in decreased alphaB-crystallin levels, as revealed by Western blot and immunocytochemical analyzes. The reduced alphaBj-crystallin expression was accompanied by alterations in cellular phenotyp :(1)a reduction of cell size and/or a slender cell mophology ; (2)a disorganized microfilament network ; and (3)a reduction of cell adhesiveness. Like HSP27, the presence of additional alphaB-crystallin protein confer a thermoresistant phenotype to stable transfectants. Thus, alphaB-crystallin inglioma cells plays a role in their thermal resistance and maycontribute to the stability of cytoskeletal organization. Next we investigated the influence of elevated extracellular K^+ on th expression of alphaB-crystallin in glial cells. The treatment of the glioma cells with augmented K^+ in the cultrue media induced an accumulation of alphaB-crystallin mRNA in a dose-dependent manner and an accumulation of the alphaB-crystallin as well. Furthermore, an overexpression of alphaB-crystallin in the transformant transfected with a rat alphaB-crystallin cDNA conferred a resistant phenotype against the insult of elevated extracellular K^+ on the glioma cells. Thus, alphaB-crystallin may contribute to the survival of reactive glia in the presence of a high extracellular K^+ concentration.