title: Isoform-specific immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human carotid and main cerebral arteries.
abstract: 14-3-3 proteins are now recognized to have a wide range of potential functions and pathological relevance, such as regulating the intercellular signal processes of differentiation, the development and growth of cells, or preventing or mediating cell apoptosis and survival by controlling the localization of potential signaling molecules. We investigated the immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human cerebral and carotid arteries using 14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the cell type localization using double immunofluorolabeling. 14-3-3 common (COM)-like immunoreactivity (IR) was intense, mainly in the foam cells and multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau, eta, and zeta (6/7) isoform-specific antibodies showed similar results to those with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies, the anti-eta isoform antibody most intensely immunolabeled multinucleated giant cells and foam cells, and the anti-zeta isoform antibody most intensely immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid plaques. Zeta IR was also observed in one part of the mural thrombus and in the nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell components, but extracellular lesions were partly positive for this isoform. In the main cerebral arteries, the anti-epsilon isoform antibody most intensely immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques. Endothelial cells were also positive for the epsilon isoform. These findings may provide a basis for understanding the isoform-specific role associated with atherosclerotic lesions of the cerebral and carotid arteries.
authors.affiliation: Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. takahiko@tokyo-med.ac.jp
authors.forename: Takahiko
authors.initials: T
authors.lastname: Umahara
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.forename: Shunichi
authors.initials: S
authors.lastname: Koyama
authors.forename: Takao
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Jiro
authors.initials: J
authors.lastname: Akimoto
authors.forename: Jo
authors.initials: J
authors.lastname: Haraoka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology; D002536:Cerebral Arteries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D020033:Protein Isoforms