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 Nε-(-γ-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.
| Original language | English |
|---|---|
| Pages (from-to) | 841-848 |
| Number of pages | 8 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 61 |
| Issue number | 10 |
| Publication status | Published - Oct 1 2002 |
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Keywords
- Chorea-Acanthocytosis
- Erythrocytes
- Muscle
- N-(-γ- glutamyl)lysine isopeptide
- tTGase
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neuroscience(all)
Cite this
Abnormal accumulation of tTgase products in muscle and erythrocytes of chorea-acanthocytosis patients. / Melone, Mariarosa A B; Di Fede, Giuseppe; Peluso, Gianfranco; Lus, Giacomo; Di Iorio, Giuseppe; Sampaolo, Simone; Capasso, Antonio; Gentile, Vittorio; Cotrufo, Roberto.
In: Journal of Neuropathology and Experimental Neurology, Vol. 61, No. 10, 01.10.2002, p. 841-848.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Abnormal accumulation of tTgase products in muscle and erythrocytes of chorea-acanthocytosis patients
AU - Melone, Mariarosa A B
AU - Di Fede, Giuseppe
AU - Peluso, Gianfranco
AU - Lus, Giacomo
AU - Di Iorio, Giuseppe
AU - Sampaolo, Simone
AU - Capasso, Antonio
AU - Gentile, Vittorio
AU - Cotrufo, Roberto
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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 Nε-(-γ-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.
AB - 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 Nε-(-γ-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.
KW - Chorea-Acanthocytosis
KW - Erythrocytes
KW - Muscle
KW - N-(-γ- glutamyl)lysine isopeptide
KW - tTGase
UR - http://www.scopus.com/inward/record.url?scp=0036792882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036792882&partnerID=8YFLogxK
M3 - Article
VL - 61
SP - 841
EP - 848
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 10
ER -