p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy.

Abstract

The apoptotic death of putaminal neurons and glia in a patient with hereditary ferritinopathy is studied immunohistochemically with antibodies to p53, activated caspase-3, PUMA, BAX, cytochrome c, and inducible nitric oxide synthase. In addition to the overexpression of ferritin and the iron accumulations assumed to result from the genetically incompetent ferritin molecule, additional contributions to the iron, heme, and hyaline deposits in this disease are sought with antibodies to 2 recently discovered globins in humans, neuroglobin and cytoglobin. The "pathognomonic" swollen to vacuolated nuclei are immunoreactive for both p53 and activated caspase-3, indicating the intervention of the p53-mediated apoptotic pathway. The immunohistochemical demonstration of neuroglobin in the swollen nuclei and both globins in the hyaline deposits highlights the potential pathogenic importance of 2 other iron-containing proteins in this disease that is largely restricted to brain. Hereditary ferritinopathy is the first human disease in which abnormalities in these heme-containing proteins are demonstrated.

• Authors: James M Powers
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 65 Issue 7 Pg. 716-21 (Jul 2006) ISSN: 0022-3069 [Print] England
• PMID: 16825958 (Publication Type: Journal Article)

Chemical References

• Nerve Tissue Proteins
• Neuroglobin
• Tumor Suppressor Protein p53
• Globins
• Ferritins
• Iron
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• Apoptosis (physiology)
• Brain (cytology, metabolism, pathology)
• Caspase 3
• Caspases (metabolism)
• Cell Nucleus (metabolism)
• Enzyme Activation
• Ferritins (metabolism)
• Globins (metabolism)
• Heredodegenerative Disorders, Nervous System (genetics, metabolism, pathology)
• Humans
• Hyalin (metabolism)
• Iron (metabolism)
• Iron Metabolism Disorders (genetics, metabolism, pathology)
• Nerve Tissue Proteins (metabolism)
• Neuroglia (cytology, metabolism, pathology)
• Neuroglobin
• Neurons (cytology, metabolism, pathology)
• Putamen (cytology, metabolism, pathology)
• Tumor Suppressor Protein p53 (genetics, metabolism)