Back to Search
Start Over
Abnormal accumulation of tTGase products in muscle and erythrocytes of chorea-acanthocytosis patients.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2002 Oct; Vol. 61 (10), pp. 841-8. - Publication Year :
- 2002
-
Abstract
- Chorea-Acanthocytosis (CHAC) is an autosomal recessive disease characterized by neurodegeneration and acanthocytosis. Enhanced creatine kinase concentration is a constant feature of the condition. The mechanism underlying CHAC is unknown. However, acanthocytosis and enhanced creatine kinase suggest a protein defect that deranges the membrane-cytoskeleton interface in erythrocytes and muscle, thereby resulting in neurodegeneration. Acanthocytes have been correlated with structural and functional changes in membrane protein band 3--a ubiquitous anion transporter. Residue Gln-30 of band 3 serves as a membrane substrate for tissue transglutaminase (tTGase), which belongs to a class of intra- and extra-cellular Ca2+-dependent cross-linking enzymes found in most vertebrate tissues. In an attempt to cast light on the pathophysiology of CHAC, we used reverse-phase HPLC and immunohistochemistry to evaluate the role of tTGase in this disorder. We found increased amounts of tTGase-derived N(epsilon)-(-gamma-glutamyl)lysine isopeptide cross-links in erythrocytes and muscle from CHAC patients. Furthermore, immunohistochemistry demonstrated abnormal accumulation of tTGase products as well as proteinaceous bodies in CHAC muscles. These findings could explain the mechanisms underlying the increased blood levels of creatine kinase and acanthocytosis, which are the most consistent features of this neurodegenerative disease.
- Subjects :
- Chorea blood
Chorea pathology
Cross-Linking Reagents
Erythrocytes pathology
Erythrocytes ultrastructure
GTP-Binding Proteins blood
Humans
Isoenzymes blood
Isoenzymes metabolism
Microscopy, Electron
Muscle, Skeletal pathology
Muscle, Skeletal ultrastructure
Peptide Mapping
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases blood
Chorea enzymology
Erythrocytes enzymology
GTP-Binding Proteins metabolism
Muscle, Skeletal enzymology
Transglutaminases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3069
- Volume :
- 61
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 12387450
- Full Text :
- https://doi.org/10.1093/jnen/61.10.841