title: Progressive ankylosis (Ank) protein is expressed by neurons and Ank immunohistochemical reactivity is increased by limbic seizures.
abstract: Ank is a 492-amino acid multipass transmembrane protein involved in the regulation of extracellular inorganic pyrophosphate levels and the control of tissue calcification. Previous Northern blot hybridization experiments revealed that Ank mRNA was expressed in the brain, but there have been no reports describing the anatomical sites or specific cell types in the brain that express Ank protein. In this study, we demonstrate that Ank is expressed primarily in human brain neurons, with the highest levels of expression observed in the thalamus, the III and V cortical layers, the Purkinje cells of the cerebellum, clusters of cells in the dorsal portion of the pons and midbrain, and neurons of the anterior horn of the spinal cord. In primary mouse neuronal cell cultures, Ank is detected on both the cell body and on cell extensions, mainly dendrites. In the rat brain, Ank mRNA is expressed at relatively high levels in the thalamus, midbrain, and spinal cord, and the Ank protein expression pattern is similar to that observed in the human brain. Finally, we observed a significant increase in Ank immunoreactivity in the rat amygdala, the CA-2 and CA-3 layers of the hippocampus, and the cerebral cortex after the induction of seizure activity. Ank regulation of ATP and/or inorganic pyrophosphate release from neurons may function to modulate the membrane excitability and cell death associated with seizure activity.
authors.affiliation: Departments of Vascular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Yepes
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moore
authors.forename: Sharron A N
authors.initials: SA
authors.lastname: Brown
authors.forename: Heather N
authors.initials: HN
authors.lastname: Hanscom
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Smith
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lawrence
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Winkles
mesh_terms: D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D015152:Blotting, Northern; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008032:Limbic System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D028061:Phosphate Transport Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C498770:ANKH protein, human; C498769:Ankh protein, mouse; D008565:Membrane Proteins; D028061:Phosphate Transport Proteins; D012333:RNA, Messenger; C410982:ank protein, mouse; D007608:Kainic Acid