Uncoupling of Oxidative Phosphorylation in Rat Liver and Spleen Mitochondria by Exposure to Total-Body Irradiation

Yost, Martha T.; Robson, Hope H.; Yost, Henry T.

doi:10.2307/3572217

Cited by 27 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After exposure, this may be accompanied by an increased affinity for O 2 that, on the one hand, produces more mtROS [10], (especially in hypoxic conditions) [31], yet, on the other hand, provides a beneficial radiotherapeutic environment for well-oxygenated non-malignant cells to repair the sub-lethal damage that usually occurs within 24 hours of exposure. Similarly, uncoupling in malignantly transformed cells has been observed for moderate doses (0.4 and 0.8 Gy) and high doses (9 and 10 Gy) of X- and α-radiation, evidenced by modified oxidation phosphorylation activity, cytochrome c oxidase and O 2 consumption per mtDNA copy number [36, 37]. Likewise, Voehringer et al [29] showed radiation-induced UCP2 activation lead to mitochondrial uncoupling and even cell death, in an irradiated murine B cell lymphoma model, although the hypothesized radiation-induced loss of membrane potential was observed by others [27, 28].…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy

Richardson

Harper

2016

Oncotarget

View full text Add to dashboard Cite

It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.

show abstract

Section: Resultsmentioning

confidence: 99%

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy

Richardson

Harper

2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…In the irradiated mice group, in the first few days after the irradiation the ATP level was replenished by short-term mechanisms of the phosphate group transfer from Pcr to ADP. After that time, the ATP replenishment became due to severe radiation damage, which causes uncoupling of oxidative phosphorylation25 ( i.e . liver damage) no longer possible thus resulting in the animal death with approximately 50% probability in 10 days after the irradiation.…”

Section: Discussionmentioning

confidence: 99%

Study of radiation induced changes of phosphorus metabolism in mice by 31P NMR spectroscopy

Serša¹,

Kranjc²,

Serša³

et al. 2010

Radiology and Oncology

View full text Add to dashboard Cite

BackgroundThe aim of this study was to examine whether 31P NMR can efficiently detect X-ray radiation induced changes of energy metabolism in mice. Exposure to ionizing radiation causes changes in energy supply that are associated with the tissue damage because of oxidative stress and uncoupled oxidative phosphorylation. This has as a consequence decreased phosphocreatine to adenosine triphosphate ratio (Pcr/ATP) as well as increased creatine kinase (CK) and liver enzymes (transaminases AST and ALT) levels in serum.Materials and methodsIn this study, experimental mice that received 7 Gy of X-ray radiation and a control group were studied by 31P NMR spectroscopy and biochemically by measuring CK and liver enzyme levels in plasma. Mice (irradiated and control) were measured at regular time intervals for the next three weeks after the exposure to radiation.ResultsA significant change in the Pcr/ATP ratio, determined from corresponding peaks of 31P NMR spectra, was observed in the 7 Gy group 2 days or more after the irradiation, while no significant change in the Pcr/ATP ratio, was observed in the control group. This result was supported by parallel measurements of CK levels that were highly increased immediately after the irradiation which correlates with the observed decrease of the Pcr/ATP ratio and with it associated drop of muscle energy supply.ConclusionsThe 31P NMR measurements of the Pcr/ATP ratio can in principle serve as an instantaneous and noninvasive index for assessment of the received dose of irradiation.

show abstract

“…All mitochondrial samples tested were conventionally isolated from the rat tissue homogenates listed below, and prepared using iron-free homogenization media, 1:4 v/w, +4 • C, in a tightly-fitting, Teflon-glass RCJ200 homogenizer with a fixed speed for the Teflon pestle rotation (Biomedlab Ltd, Minsk, Republic of Byelorussia), adjusting the 7.8-8.4 pH range with either HEPES or Tris-based buffer systems containing 2.5 mM EDTA, 1.5 mM NaCl, 0.25 M sucrose, 0.1% glutathione, 0.001% soy bean trypsin inhibitor as specified in [7][8][9][10][11][12]; 800-15,000 × g centrifugation of homogenates was performed at +4 • C (Spinco L5-85B Ultracentrifuge, rotor SW40, Beckman, Austria). These procedures were specifically adapted for each of the particular rat tissues studied: spleen [7], liver [8], skeletal muscles [9], heart muscle [10], kidneys [11], and brain [12].…”

Section: Isolation Of Mitochondriamentioning

confidence: 99%

The tissue-specific “ferromagnetic attack” on hyperactivation of ATP synthesis by magnesium-25 in mitochondria

Shatalov

Svistunov²,

Napolov³

et al. 2012

Magnesium Research

View full text Add to dashboard Cite

A 25 Mg 2+-operated hyper-activation of ATP synthesis has been investigated in mitochondria (Mt) isolated from iron-rich and iron-poor rat tissues: spleen, liver, skeletal muscle, myocardium, kidneys, brain. Both magnetic (25 Mg) and non-magnetic (24 Mg) magnesium isotopes were separately administered to estimate the degree of the ATP production related to the magnetic isotope effect (MIE) of 25 Mg 2+ as a function of the amount of Mt-endogenous iron ions. A strong but negative (r =-0.88) correlation between the 25 Mg-MIE degree and the Mt[Fe 2+ ] values was found. The physical and biophysical mechanisms behind these phenomena, as well as the possible impact of these data on further biochemical and pharmacological studies involving 25 Mg-promoted nuclear spin selectivity in mitochondrial function, are under discussion.

show abstract

Uncoupling of Oxidative Phosphorylation in Rat Liver and Spleen Mitochondria by Exposure to Total-Body Irradiation

Cited by 27 publications

References 13 publications

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy

Study of radiation induced changes of phosphorus metabolism in mice by 31P NMR spectroscopy

The tissue-specific “ferromagnetic attack” on hyperactivation of ATP synthesis by magnesium-25 in mitochondria

Contact Info

Product

Resources

About