Cerebellar expression of copper chaperone for superoxide, cytosolic cu/ n-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock rotein 32 in patients with menkes kinky hair disease

Immunohistochemical tudy

Atsushi Yokoyama, Kousaku Ohno, Asao Hirano, Masayuki Shintaku, Masako Kato, Kazuhiko Hayashi, Shinsuke Kato

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Znsuperoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein (hsp) 32. Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.

Original languageEnglish (US)
Pages (from-to)23-35
Number of pages13
JournalYonago Acta Medica
Volume57
Issue number1
StatePublished - 2014

Fingerprint

Menkes Kinky Hair Syndrome
Acrolein
Purkinje Cells
Superoxides
Superoxide Dismutase
Copper
Shock
Hot Temperature
Heat-Shock Proteins
Dendrites
Oxidative Stress
4-hydroxy-2-nonenal
Cell Death
Cactaceae
Salix
Axons
Anti-Idiotypic Antibodies
Autopsy

Keywords

  • Copper chaperone for superoxide
  • Cytosolic cu/zn-superoxide dismutase
  • Immunohistochemistry
  • Menkes kinky hair disease
  • Purkinje cell

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cerebellar expression of copper chaperone for superoxide, cytosolic cu/ n-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock rotein 32 in patients with menkes kinky hair disease : Immunohistochemical tudy. / Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke.

In: Yonago Acta Medica, Vol. 57, No. 1, 2014, p. 23-35.

Research output: Contribution to journalArticle

Yokoyama, Atsushi ; Ohno, Kousaku ; Hirano, Asao ; Shintaku, Masayuki ; Kato, Masako ; Hayashi, Kazuhiko ; Kato, Shinsuke. / Cerebellar expression of copper chaperone for superoxide, cytosolic cu/ n-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock rotein 32 in patients with menkes kinky hair disease : Immunohistochemical tudy. In: Yonago Acta Medica. 2014 ; Vol. 57, No. 1. pp. 23-35.
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title = "Cerebellar expression of copper chaperone for superoxide, cytosolic cu/ n-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock rotein 32 in patients with menkes kinky hair disease: Immunohistochemical tudy",
abstract = "Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Znsuperoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein (hsp) 32. Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50{\%} of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23{\%}. Approximately 56{\%}, 42{\%} and 40{\%} of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50{\%} of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.",
keywords = "Copper chaperone for superoxide, Cytosolic cu/zn-superoxide dismutase, Immunohistochemistry, Menkes kinky hair disease, Purkinje cell",
author = "Atsushi Yokoyama and Kousaku Ohno and Asao Hirano and Masayuki Shintaku and Masako Kato and Kazuhiko Hayashi and Shinsuke Kato",
year = "2014",
language = "English (US)",
volume = "57",
pages = "23--35",
journal = "Yonago Acta Medica",
issn = "0513-5710",
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TY - JOUR

T1 - Cerebellar expression of copper chaperone for superoxide, cytosolic cu/ n-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock rotein 32 in patients with menkes kinky hair disease

T2 - Immunohistochemical tudy

AU - Yokoyama, Atsushi

AU - Ohno, Kousaku

AU - Hirano, Asao

AU - Shintaku, Masayuki

AU - Kato, Masako

AU - Hayashi, Kazuhiko

AU - Kato, Shinsuke

PY - 2014

Y1 - 2014

N2 - Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Znsuperoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein (hsp) 32. Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.

AB - Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Znsuperoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein (hsp) 32. Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.

KW - Copper chaperone for superoxide

KW - Cytosolic cu/zn-superoxide dismutase

KW - Immunohistochemistry

KW - Menkes kinky hair disease

KW - Purkinje cell

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JO - Yonago Acta Medica

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