Koyama Y, Goldman J E
Department of Pathology and the Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Am J Pathol. 1999 May;154(5):1563-72. doi: 10.1016/s0002-9440(10)65409-0.
In several neuropathological conditions, alphaB-crystallin and glial fibrillary acidic protein (GFAP) accumulate and form cytoplasmic inclusions in astrocytes. To explore the pathogenesis of the inclusions and the possible functions of the accumulated alphaB-crystallin, GFAP and alphaB-crystallin were overexpressed in cultured astrocytes by transient transfection. Human GFAP formed filamentous, cytoplasmic inclusions in mouse astrocytes, NIH3T3 cells, rat C6 glioma cells, and human U251 glioma cells. These human GFAP inclusions did not contain the endogenous vimentin or beta-tubulin, and the intermediate filament and microtubular networks of the transfected cells appeared normal. alphaB-crystallin and hsp25 were associated with the GFAP inclusions. Increasing intracellular alphaB-crystallin levels using recombinant adenoviruses, either before or after GFAP inclusions were formed, decreased the number of inclusion-bearing astrocytes and converted the human GFAP from an inclusion to a spread, filamentous form. These results suggest that alphaB-crystallin reorganizes abnormal intermediate filament aggregates into the normal filamentous network.
在几种神经病理学情况下，αB-晶状体蛋白和胶质纤维酸性蛋白（GFAP）会积聚并在星形胶质细胞中形成细胞质包涵体。为了探究这些包涵体的发病机制以及积聚的αB-晶状体蛋白的可能功能，通过瞬时转染在培养的星形胶质细胞中过表达GFAP和αB-晶状体蛋白。人GFAP在小鼠星形胶质细胞、NIH3T3细胞、大鼠C6胶质瘤细胞和人U251胶质瘤细胞中形成丝状细胞质包涵体。这些人GFAP包涵体不包含内源性波形蛋白或β-微管蛋白，并且转染细胞的中间丝和微管网络看起来正常。αB-晶状体蛋白和hsp25与GFAP包涵体相关。在GFAP包涵体形成之前或之后使用重组腺病毒增加细胞内αB-晶状体蛋白水平，可减少含包涵体星形胶质细胞的数量，并将人GFAP从包涵体形式转变为分散的丝状形式。这些结果表明，αB-晶状体蛋白将异常的中间丝聚集体重新组织成正常的丝状网络。
