Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity Is Decreased in Multiple Sclerosis Patients

Effects of β-Interferon Treatment

Iain Hargreaves, Nimesh Mody, John Land, Simon Heales

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment.

METHODS: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls.

RESULTS: MRC Complex IV activity was found to be significantly decreased (p< 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls.

CONCLUSIONS: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.

Original languageEnglish
Article number36
JournalJournal of Clinical Medicine
Volume7
Issue number2
DOIs
Publication statusPublished - 20 Feb 2018

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Electron Transport
Interferons
Multiple Sclerosis
Blood Cells
Therapeutics
Oxidative Stress
Cytochrome-c Oxidase Deficiency
Enzyme Assays

Keywords

  • Journal Article
  • mitochondrial respiratory chain
  • complex IV
  • blood mononuclear cells
  • multiple sclerosis
  • β-Interferon

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Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity Is Decreased in Multiple Sclerosis Patients : Effects of β-Interferon Treatment. / Hargreaves, Iain; Mody, Nimesh; Land, John; Heales, Simon.

In: Journal of Clinical Medicine, Vol. 7, No. 2, 36, 20.02.2018.

Research output: Contribution to journalArticle

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title = "Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity Is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment",
abstract = "OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment.METHODS: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls.RESULTS: MRC Complex IV activity was found to be significantly decreased (p< 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls.CONCLUSIONS: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.",
keywords = "Journal Article, mitochondrial respiratory chain, complex IV, blood mononuclear cells, multiple sclerosis, β-Interferon",
author = "Iain Hargreaves and Nimesh Mody and John Land and Simon Heales",
note = "Acknowledgments: We acknowledge the invaluable help of Dr. Peter Rudge, Consultant Neurologist, National Hospital, Queen Square London, for his help with patient recruitment. We also gratefully acknowledge financial support from the National Institute for Health Research, Biomedical Research Centre.",
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T2 - Effects of β-Interferon Treatment

AU - Hargreaves, Iain

AU - Mody, Nimesh

AU - Land, John

AU - Heales, Simon

N1 - Acknowledgments: We acknowledge the invaluable help of Dr. Peter Rudge, Consultant Neurologist, National Hospital, Queen Square London, for his help with patient recruitment. We also gratefully acknowledge financial support from the National Institute for Health Research, Biomedical Research Centre.

PY - 2018/2/20

Y1 - 2018/2/20

N2 - OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment.METHODS: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls.RESULTS: MRC Complex IV activity was found to be significantly decreased (p< 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls.CONCLUSIONS: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.

AB - OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment.METHODS: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls.RESULTS: MRC Complex IV activity was found to be significantly decreased (p< 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls.CONCLUSIONS: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.

KW - Journal Article

KW - mitochondrial respiratory chain

KW - complex IV

KW - blood mononuclear cells

KW - multiple sclerosis

KW - β-Interferon

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DO - 10.3390/jcm7020036

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VL - 7

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

SN - 2077-0383

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