Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes

Gary Fiskum, Camelia A. Danilov, Zara Mehrabian, Linda L. Bambrick, Tibor Kristian, Mary C. McKenna, Irene Hopkins, Erica Richards, Robert E. Rosenthal

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Oxidative stress and mitochondrial dysfunction have been closely associated in many subcellular, cellular, animal, and human studies of both acute brain injury and neurodegenerative diseases. Our animal models of brain injury caused by cardiac arrest illustrate this relationship and demonstrate that both oxidative molecular modifications and mitochondrial metabolic impairment are exacerbated by reoxygenation of the brain using 100% ventilatory O2 compared to lower levels that maintain normoxemia. Numerous molecular mechanisms may be responsible for mitochondrial dysfunction caused by oxidative stress, including oxidation and inactivation of mitochondrial proteins, promotion of the mitochondrial membrane permeability transition, and consumption of metabolic cofactors and intermediates, for example, NAD(H). Moreover, the relative contribution of these mechanisms to cell injury and death is likely different among different types of brain cells, for example, neurons and astrocytes. In order to better understand these oxidative stress mechanisms and their relevance to neurologic disorders, we have undertaken studies with primary cultures of astrocytes and neurons exposed to O2 and glucose deprivation and reoxygenation and compared the results of these studies to those using a rat model of neonatal asphyxic brain injury. These results support the hypothesis that release and or consumption of mitochondrial NAD(H) is at least partially responsible for respiratory inhibition, particularly in neurons.

Original languageEnglish (US)
Title of host publicationMitochondria and Oxidative Stress in Neurodegenerative Disorders
Pages129-138
Number of pages10
Volume1147
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1147
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Fingerprint

Oxidative stress
Astrocytes
Brain Injuries
Neurons
Brain
Oxidative Stress
NAD
Mitochondrial Proteins
Mitochondrial Membranes
Brain Diseases
Heart Arrest
Nervous System Diseases
Animals
Neurodegenerative Diseases
Permeability
Neurodegenerative diseases
Cell Death
Animal Models
Glucose
Wounds and Injuries

Keywords

  • Nicotinamide adenine dinucleotide
  • Pyruvate dehydrogenase
  • Respiration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Fiskum, G., Danilov, C. A., Mehrabian, Z., Bambrick, L. L., Kristian, T., McKenna, M. C., ... Rosenthal, R. E. (2008). Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. In Mitochondria and Oxidative Stress in Neurodegenerative Disorders (Vol. 1147, pp. 129-138). (Annals of the New York Academy of Sciences; Vol. 1147). https://doi.org/10.1196/annals.1427.026

Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. / Fiskum, Gary; Danilov, Camelia A.; Mehrabian, Zara; Bambrick, Linda L.; Kristian, Tibor; McKenna, Mary C.; Hopkins, Irene; Richards, Erica; Rosenthal, Robert E.

Mitochondria and Oxidative Stress in Neurodegenerative Disorders. Vol. 1147 2008. p. 129-138 (Annals of the New York Academy of Sciences; Vol. 1147).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Fiskum, G, Danilov, CA, Mehrabian, Z, Bambrick, LL, Kristian, T, McKenna, MC, Hopkins, I, Richards, E & Rosenthal, RE 2008, Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. in Mitochondria and Oxidative Stress in Neurodegenerative Disorders. vol. 1147, Annals of the New York Academy of Sciences, vol. 1147, pp. 129-138. https://doi.org/10.1196/annals.1427.026
Fiskum G, Danilov CA, Mehrabian Z, Bambrick LL, Kristian T, McKenna MC et al. Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. In Mitochondria and Oxidative Stress in Neurodegenerative Disorders. Vol. 1147. 2008. p. 129-138. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1427.026
Fiskum, Gary ; Danilov, Camelia A. ; Mehrabian, Zara ; Bambrick, Linda L. ; Kristian, Tibor ; McKenna, Mary C. ; Hopkins, Irene ; Richards, Erica ; Rosenthal, Robert E. / Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. Mitochondria and Oxidative Stress in Neurodegenerative Disorders. Vol. 1147 2008. pp. 129-138 (Annals of the New York Academy of Sciences).
@inproceedings{afde31fccf4a4cf2bedd843776384fe1,
title = "Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes",
abstract = "Oxidative stress and mitochondrial dysfunction have been closely associated in many subcellular, cellular, animal, and human studies of both acute brain injury and neurodegenerative diseases. Our animal models of brain injury caused by cardiac arrest illustrate this relationship and demonstrate that both oxidative molecular modifications and mitochondrial metabolic impairment are exacerbated by reoxygenation of the brain using 100{\%} ventilatory O2 compared to lower levels that maintain normoxemia. Numerous molecular mechanisms may be responsible for mitochondrial dysfunction caused by oxidative stress, including oxidation and inactivation of mitochondrial proteins, promotion of the mitochondrial membrane permeability transition, and consumption of metabolic cofactors and intermediates, for example, NAD(H). Moreover, the relative contribution of these mechanisms to cell injury and death is likely different among different types of brain cells, for example, neurons and astrocytes. In order to better understand these oxidative stress mechanisms and their relevance to neurologic disorders, we have undertaken studies with primary cultures of astrocytes and neurons exposed to O2 and glucose deprivation and reoxygenation and compared the results of these studies to those using a rat model of neonatal asphyxic brain injury. These results support the hypothesis that release and or consumption of mitochondrial NAD(H) is at least partially responsible for respiratory inhibition, particularly in neurons.",
keywords = "Nicotinamide adenine dinucleotide, Pyruvate dehydrogenase, Respiration",
author = "Gary Fiskum and Danilov, {Camelia A.} and Zara Mehrabian and Bambrick, {Linda L.} and Tibor Kristian and McKenna, {Mary C.} and Irene Hopkins and Erica Richards and Rosenthal, {Robert E.}",
year = "2008",
month = "12",
day = "1",
doi = "10.1196/annals.1427.026",
language = "English (US)",
isbn = "9781573317139",
volume = "1147",
series = "Annals of the New York Academy of Sciences",
pages = "129--138",
booktitle = "Mitochondria and Oxidative Stress in Neurodegenerative Disorders",

}

TY - GEN

T1 - Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes

AU - Fiskum, Gary

AU - Danilov, Camelia A.

AU - Mehrabian, Zara

AU - Bambrick, Linda L.

AU - Kristian, Tibor

AU - McKenna, Mary C.

AU - Hopkins, Irene

AU - Richards, Erica

AU - Rosenthal, Robert E.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Oxidative stress and mitochondrial dysfunction have been closely associated in many subcellular, cellular, animal, and human studies of both acute brain injury and neurodegenerative diseases. Our animal models of brain injury caused by cardiac arrest illustrate this relationship and demonstrate that both oxidative molecular modifications and mitochondrial metabolic impairment are exacerbated by reoxygenation of the brain using 100% ventilatory O2 compared to lower levels that maintain normoxemia. Numerous molecular mechanisms may be responsible for mitochondrial dysfunction caused by oxidative stress, including oxidation and inactivation of mitochondrial proteins, promotion of the mitochondrial membrane permeability transition, and consumption of metabolic cofactors and intermediates, for example, NAD(H). Moreover, the relative contribution of these mechanisms to cell injury and death is likely different among different types of brain cells, for example, neurons and astrocytes. In order to better understand these oxidative stress mechanisms and their relevance to neurologic disorders, we have undertaken studies with primary cultures of astrocytes and neurons exposed to O2 and glucose deprivation and reoxygenation and compared the results of these studies to those using a rat model of neonatal asphyxic brain injury. These results support the hypothesis that release and or consumption of mitochondrial NAD(H) is at least partially responsible for respiratory inhibition, particularly in neurons.

AB - Oxidative stress and mitochondrial dysfunction have been closely associated in many subcellular, cellular, animal, and human studies of both acute brain injury and neurodegenerative diseases. Our animal models of brain injury caused by cardiac arrest illustrate this relationship and demonstrate that both oxidative molecular modifications and mitochondrial metabolic impairment are exacerbated by reoxygenation of the brain using 100% ventilatory O2 compared to lower levels that maintain normoxemia. Numerous molecular mechanisms may be responsible for mitochondrial dysfunction caused by oxidative stress, including oxidation and inactivation of mitochondrial proteins, promotion of the mitochondrial membrane permeability transition, and consumption of metabolic cofactors and intermediates, for example, NAD(H). Moreover, the relative contribution of these mechanisms to cell injury and death is likely different among different types of brain cells, for example, neurons and astrocytes. In order to better understand these oxidative stress mechanisms and their relevance to neurologic disorders, we have undertaken studies with primary cultures of astrocytes and neurons exposed to O2 and glucose deprivation and reoxygenation and compared the results of these studies to those using a rat model of neonatal asphyxic brain injury. These results support the hypothesis that release and or consumption of mitochondrial NAD(H) is at least partially responsible for respiratory inhibition, particularly in neurons.

KW - Nicotinamide adenine dinucleotide

KW - Pyruvate dehydrogenase

KW - Respiration

UR - http://www.scopus.com/inward/record.url?scp=57649183364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57649183364&partnerID=8YFLogxK

U2 - 10.1196/annals.1427.026

DO - 10.1196/annals.1427.026

M3 - Conference contribution

C2 - 19076438

AN - SCOPUS:57649183364

SN - 9781573317139

VL - 1147

T3 - Annals of the New York Academy of Sciences

SP - 129

EP - 138

BT - Mitochondria and Oxidative Stress in Neurodegenerative Disorders

ER -