Mitochondrial hydrogen peroxide generation by NADH-oxidase activity following regional myocardial ischemia in the dog

Vandeplassche, G; Hermans, Carlo; Thoné, Fred; Borgers, M.

doi:10.1016/0022-2828(89)90649-4

Cited by 53 publications

(17 citation statements)

References 37 publications

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“…In that study, a close relationship between their findings and an oxygenmediated process was suggested, although the source of oxidants were not identified. An increase in peroxide production after reperfusion has been described by several authors (21)(22)(23). In the present study, we have found several indices of oxidative stress elevated in mitochondria as well as in heart homogenate, such as GSSG and protein carbonyls.…”

Section: Discussionmentioning

confidence: 95%

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

Serviddio¹,

Venosa

Federici

et al. 2005

FASEB j.

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Several recent works have shown that a brief ischemia applied during the onset of reperfusion (postconditioning) is cardioprotective in different animal models and that the early minutes of reperfusion are critical to its cardioprotection. This effect has been related to prevention of oxidative stress, but mechanisms have not been clearly demonstrated. The present study tested the hypothesis that mitochondria play a central role in peroxide production and oxidative stress during reperfusion and are responsible for the protective effect of postconditioning. Isolated perfused rat hearts were subjected to complete global ischemia for 45 min and reperfused for 40 min. Normoxic group was reperfused with a Krebs-Henseleit solution with the preischemic pO2 level (600 mmHg); in the "hypoxic group," normoxic reperfusion was preceded by 3 min with 150 mmHg pO2. Reperfusion was stopped at 3 and 40 min. The rate of hydroperoxide production, GSH, GSSG, and carbonyl protein levels were measured in mitochondria at 3 min and at the end of reperfusion. GSH and GSSG were also measured in tissue. Hemodinamic function was monitored during the experiment. LVEDp increased and LVDp decreased in the normoxic group but not in the hypoxic group. The rate of mitochondrial peroxide production was higher in normoxic than in the hypoxic group 3 min after reperfusion and at its conclusion. Accordingly, GSH was oxidized in normoxic but not in hypoxic hearts. Mitochondria carbonyl proteins were significantly higher in normoxic than in the hypoxic group at the end of reperfusion. In this model, 1) hypoxic reperfusion at the onset of reperfusion reduces myocardial injury; 2) the major rate of mitochondrial peroxide production is 3 min after the onset of reperfusion; 3) cardioprotection of postconditioning correlates with reduced mitochondria peroxide production and prevention of GSH oxidation.

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Section: Discussionmentioning

confidence: 95%

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

Serviddio¹,

Venosa

Federici

et al. 2005

FASEB j.

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“…Our results contribute to delineating the involvement of cryAB in the intrinsic and ER stress pathway of apoptosis activated by ROS-induced oxidative damage. ROS are known to play a major role in the pathogenesis of myocardial dysfunction in a variety of conditions, including I/R injury (16), with H 2 O 2 playing a significant role in oxidative stress injury (39). Therefore, determining where in the apoptotic cascade cryAB intervenes to prevent H 2 O 2 injury can have therapeutic implications for cardiac disease.…”

Section: Discussionmentioning

confidence: 99%

“…Ischemia or other stresses that mimic ischemia activate the intrinsic apoptotic pathway, leading to the opening of the mitochondrial permeability transition pore (MPTP) and further downstream apoptotic events, culminating in cellular demise (11). Global ischemia as well as reperfusion have been associated with significant increases in ROS, including myocardial H 2 O 2 content (37), which plays a significant role in oxidative stress injury (39). H 2 O 2 also leads to apoptosis in CMs, by activating the intrinsic pathway of apoptosis (41), and thus makes H 2 O 2 a very good in vitro model of I/R injury.…”

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confidence: 99%

α-Crystallin B prevents apoptosis after H₂O₂ exposure in mouse neonatal cardiomyocytes

Chis

Sharma

Bousette

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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α-Crystallin B (cryAB) is the most abundant small heat shock protein in cardiomyocytes (CMs) and has been shown to have potent antiapoptotic properties. Because the mechanism by which cryAB prevents apoptosis has not been fully characterized, we examined its protective effects at the cellular level by silencing cryAB in mouse neonatal CMs using lentivector-mediated transduction of short hairpin RNAs. Subcellular fractionation of whole hearts showed that cryAB is cytosolic under control conditions, and after H(2)O(2) exposure, it translocates to the mitochondria. Phosphorylated cryAB (PcryAB) is mainly associated with the mitochondria, and any residual cytosolic PcryAB translocates to the mitochondria after H(2)O(2) exposure. H(2)O(2) exposure caused increases in cryAB and PcryAB levels, and cryAB silencing resulted in increased levels of apoptosis after exposure to H(2)O(2). Coimmunoprecipitation assays revealed an apparent interaction of both cryAB and PcryAB with mitochondrial voltage-dependent anion channels (VDAC), translocase of outer mitochondrial membranes 20 kDa (TOM 20), caspase 3, and caspase 12 in mouse cardiac tissue. Our results are consistent with the conclusion that the cardioprotective effects of cryAB are mediated by its translocation from the cytosol to the mitochondria under conditions of oxidative stress and that cryAB interactions with VDAC, TOM 20, caspase 3, and caspase 12 may be part of its protective mechanism.

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“…Apart from xanthine oxidase mediated degradation of hypoxanthine (9), and circulating neutrophils (19), it has recently been shown that the mitochondrial enzyme, NADH-oxidase is a potent oxygen-dcrived radical generator in heart mitochondria (17). Furthermore, the activity of the cnzymc was increased in viable ischcmic areas (21,22).…”

Section: Discussionmentioning

confidence: 98%

Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

et al. 1990

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The role of Ca2+ in the pathogenesis leading to ischemic myocardial cell death is still controversial. To gain insight into this phenomenon a cytochemical procedure, the phosphate pyroantimonate method, was used to localize different subcellular Ca2(+)-pools at the ultrastructural level. After 45 min of left anterior descending coronary artery (LAD) occlusion, the coronary arteries were perfused with triphenyltetrazoliumchloride staining (TTC) to identify viable ischemic and infarcted tissue. In non-ischemic tissue, Ca2(+)-deposits were confined to the sarcolemma, sarcolemma-derived vesicles, transverse tubules, and intercalated disks. In infarcted tissue (TTC-negative), the sarcolemma lost its Ca2(+)-binding capacity and mitochondria were either overloaded with Ca2(+)-precipitate or they contained amorphous densities. In viable ischemic areas (determined with the TTC-technique) the sarcolemma was virtually devoid of Ca2(+)-deposits. Mitochondria in this area frequently showed clumping of the cristae, associated with an accumulation of Ca2(+)-precipitate in between the clustered cristae. The results of this study indicate that Ca2(+)-shifts occur in ischemic myocardial cells before the occurrence of other ultrastructural signs of irreversible injury which, therefore, narrows the possibility that Ca2(+)-overload is only a consequence of ischemic cell death.

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Mitochondrial hydrogen peroxide generation by NADH-oxidase activity following regional myocardial ischemia in the dog

Cited by 53 publications

References 37 publications

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

α-Crystallin B prevents apoptosis after H₂O₂ exposure in mouse neonatal cardiomyocytes

Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

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Mitochondrial hydrogen peroxide generation by NADH-oxidase activity following regional myocardial ischemia in the dog

Cited by 53 publications

References 37 publications

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia‐reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion

α-Crystallin B prevents apoptosis after H2O2 exposure in mouse neonatal cardiomyocytes

Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

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α-Crystallin B prevents apoptosis after H₂O₂ exposure in mouse neonatal cardiomyocytes