Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX

Mik, Egbert G.; Stap, Jan; Sinaasappel, M.; Beek, Hans van; Aten, Jacob A.; Leeuwen, Ton G. van; İnce, Can

doi:10.1038/nmeth940

Cited by 147 publications

(192 citation statements)

References 29 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…Future research should aim to elucidate the mechanisms that lead from decreased O 2 supply to changes in O 2 consumption, and to determine how adaptive or damaging their respective contributions are in the setting of renal I/R. Our group recently developed a method for measuring mitochondrial pO 2 in living cells in vitro by the excitation of endogenous mitochondrial protoporphyrin IX and measurement of the decay of delayed fluorescence (170). If this method proves to be feasible in vivo, it will allow insight into the balance between oxygen supply and oxygen utilization at the intracellular level.…”

Section: Mitochondrial Activity and No-mediated O 2 Consumptionmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

Self Cite

238

169

View full text Add to dashboard Cite

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

show abstract

Section: Mitochondrial Activity and No-mediated O 2 Consumptionmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

Self Cite

238

169

View full text Add to dashboard Cite

show abstract

“…Recently, it has been reported that the endogenous PpIX selectively accumulates in mitochondria and its delayed fluorescence can be used as an oxygen probe. (Mik et al, 2006) Thus, PpIX as an oxygen probe is also promising and our method is applicable to the PpIX measurements. Consequently, the oxygen concentration change inside the cell at different locations in the organ is possibly measured by this method.…”

Section: Discussionmentioning

confidence: 94%

“…(Nishimura et al, 2007) On the other hand, the new possibility using the delayed fluorescence of endogenous protoporphyrin IX (PpIX) for the oxygen monitoring in cells has been demonstrated. (Mik et al, 2006) These indicate a possibility of the decay analysis for the oxygen dynamics measurement in the cellular level.…”

Section: Introductionmentioning

confidence: 91%

Phosphorescence decay time measurements using intensity correlation spectroscopy

Nishimura

Pack

Tamura

2007

Experimental and Molecular Pathology

View full text Add to dashboard Cite

In this paper, we report on a phosphorescence measurements for oxygen dynamics in cells by means of a correlation method, which is an expansion of the fluorescence correlation spectroscopy.The intensity correlation function of the emission excited by a pulsed light source was measured.With changing the pulse timing, both the fluorescence correlation function and the decay time of phosphorescence could be analyzed. This method was applied for the analysis of the oxygen dynamics in HeLa cells stained by Pd(II)-porphine. The decay function consisted of two exponential components, which might be attributed to free and protein-bound forms of Pd(II)-porphine in the cell, respectively. The relative change of the oxygen concentration under normal and uncoupled respiration conditions was also measured. The simplicity of this method is a great advantage in the biological applications. Although the current system we used was limited in the temporal resolution, the method is in principal applicable to faster decay time measurements down to the nano-second range of the fluorescence decay times.

show abstract

“…5‐ALA is an endogenous amino acid, which is usually synthesized from glycine and succinyl CoA in mitochondria. Induced by supplementation of 5‐ALA in mitochondrion, endogenous porphyrins biosynthesis occurs through several enzyme‐catalyzed steps in cytosol and mitochondrion 6. On the other hand, following systemic administration, exogenous 5‐ALA can also be metabolized into PPIX via the same biosynthesis pathway 7.…”

Section: Introductionmentioning

confidence: 99%

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

Zeng

Zhang

et al. 2015

Advanced Science

View full text Add to dashboard Cite

The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects.

show abstract

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX

Cited by 147 publications

References 29 publications

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Phosphorescence decay time measurements using intensity correlation spectroscopy

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

Contact Info

Product

Resources

About