Superoxide production during ischemia–reperfusion in the perfused rat heart: A comparison of two methods of measurement

Näpänkangas, Juha; Liimatta, Erkki; Joensuu, Päivi; Bergmann, Ulrich; Ylitalo, Kari; Hassinen, Ilmo E.

doi:10.1016/j.yjmcc.2012.09.011

Cited by 23 publications

(25 citation statements)

References 76 publications

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“…As noted above, another potential artefact that might interfere with fluorescent measurements during ischemia and reperfusion is a change in the internal filtering exerted by myoglobin and cytochromes absorbance as they undergo oxygenation / de-oxygenation and oxidation / reduction [17,29]. The most intense absorbance by oxymyoglobin and deoxymyoglobin (absorbance maxima at 420 and 440 nm respectively [30]) occurs outside the range of all dyes used except for Indo-1, and in this case the 405/485 nm emission ratio was employed.…”

Section: Resultsmentioning

confidence: 99%

“…However, major concerns have been expressed over the use of DHE as a ROS probe, both in terms of whether the fluorescent species monitored really detects superoxide [16] and its sensitivity to changes in mitochondrial membrane potential [17]. The luminescent probe lucigenin has also been employed which did detect a large increase in ROS during reperfusion, but this only reached a peak after about 5 min of reperfusion [17] which is after mPTP opening [1,2]. Others have used multi-photon microscopy to measure changes of [Ca 2+ ] and ROS in the perfused heart [18], but in these studies pharmacological inhibition of contractile function was required.…”

Section: Introductionmentioning

confidence: 99%

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Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning

et al. 2016

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Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(P)H and flavoproteins on reperfusion (detected using autofluorescence) was rapid (t0.5 < 15 s) and significantly slower following ischemic preconditioning (IP). This argues against superoxide production from reduced Complex 1 being a critical mediator of initial mPTP opening during early reperfusion. Furthermore, MitoPY1 (a mitochondria-targeted H2O2-sensitive fluorescent probe) and aconitase activity measurements failed to detect matrix ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2–3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA) and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1) increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2–3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that IP may inhibit initial mPTP opening by alternative mechanisms such as prevention of hexokinase 2 dissociation from mitochondria during ischemia.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning

et al. 2016

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“…Changes in MMP-controlled matrix remodeling lead to increased superoxide anion free radical (Herlein et al, 2011). Matrix remodeling to the condensed state results in crystal unfolding and exposes cytochrome c to the intermembrane space facilitating superoxide anion free radical increased during the injury on mitochondria (Gupta et al, 2009;Näpänkangas et al, 2012). Excessive generation of superoxide anion free radical amounts can break the balance in cellular reductionoxidation (redox) and disrupt normal cellular functions.…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone protects against adriamycin-induced mitochondrial dysfunction in cardiomyocytes

Zhang

Chen

et al. 2015

Pharmaceutical Biology

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Results: 50 mg/kg CRY significantly promoted the energy production of ATP (16.99 ± 2.38 nmol/g Pro) (Pro: Protein) by increasing the complexes activities except II (p40.05). After the treatment of CRY, the suppressed MMP was increased while superoxide anion free radical (0.57 ± 0.07/mg Pro) was inhibited markedly. Mitochondrial biogenesis-relative factors PGC-1a, NRF-1, and TFAM were also promoted. Remarkable augmentations of NO, inducible nitric oxide synthase (iNOS), and increased activity of GSH-PX (p50.05) were also detected after the treatment of CRY, while no obvious changes on the activity of nitric oxide synthase (cNOS; p40.05) were observed. Discussion and conclusion: These results suggest that CRY protects against ADR-induced mitochondrial dysfunction in cardiomyocytes. It could be an ideal potential drug of cardioprotection.

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“…), causing tissue damage and dysfunction and/or cell death [28,29]. Furthermore, mtROS may further damage mitochondrial structure and impair function [30], leading to a vicious cycle [29,30]. Therefore, prevention of mtROS production or neutralization of the reactive molecules may prove be the most efficacious intervention against IR injury.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle

Wilson

Drake

Cui

et al. 2018

Free Radical Biology and Medicine

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Deterioration of neuromuscular junction (NMJ) integrity and function is causal to muscle atrophy and frailty, ultimately hindering quality of life and increasing the risk of death. In particular, NMJ is vulnerable to ischemia reperfusion (IR) injury when blood flow is restricted followed by restoration. However, little is known about the underlying mechanism(s) and hence the lack of effective interventions. New evidence suggests that mitochondrial oxidative stress plays a causal role in IR injury, which can be precluded by enhancing mitochondrial protein S-nitrosation (SNO). To elucidate the role of IR and mitochondrial protein SNO in skeletal muscle, we utilized a clinically relevant model and showed that IR resulted in significant muscle and motor nerve injuries with evidence of elevated muscle creatine kinase in the serum, denervation at NMJ, myofiber degeneration and regeneration, as well as muscle atrophy. Interestingly, we observed that neuromuscular transmission improved prior to muscle recovery, suggesting the importance of the motor nerve in muscle functional recovery. Injection of a mitochondria-targeted S-nitrosation enhancing agent, MitoSNO, into ischemic muscle prior to reperfusion reduced mitochondrial oxidative stress in the motor nerve and NMJ, attenuated denervation at NMJ, and resulted in accelerated functional recovery of the muscle. These findings demonstrate that enhancing mitochondrial protein SNO protects against IR-induced denervation at NMJ in skeletal muscle and accelerates functional regeneration. This could be an efficacious intervention for protecting neuromuscular injury under the condition of IR and other related pathological conditions.

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Superoxide production during ischemia–reperfusion in the perfused rat heart: A comparison of two methods of measurement

Cited by 23 publications

References 76 publications

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning

Cryptotanshinone protects against adriamycin-induced mitochondrial dysfunction in cardiomyocytes

Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle

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