Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury

Zhu, Wuqiang; Xie, Yan; Chen, Le; Yang, Huang‐Tian; Zhou, Zhao-Nian

doi:10.1016/j.yjmcc.2005.09.016

Cited by 63 publications

(73 citation statements)

References 33 publications

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“…The multiple brief exposures of hypoxia/reoxygenation in an intermittent hypoxia (IH) are comparable with ischemia/ reperfusion and exert protective effects similar to those observed in ischemic preconditioning [3][4][5][6]. It was demonstrated that IH adaptation helps to prevent mitochondrial DNA deletion and preserve mitochondrial ultrastructure [3], as well as to improve energy production in metabolic processes by increasing formation of…”

Section: Introductionmentioning

confidence: 92%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

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Abstract:The purpose of this study was to compare the influence of two regimes of intermittent hypoxia (IH) [repetitive 5 cycles of 5 min hypoxia (7% O 2 or 12% O 2 in N 2 ) followed by 15 min normoxia, daily for three weeks] on oxidative stress protective systems in liver mitochondria. To estimate the effectiveness of hypoxia adaptation at the early and late preconditioning period, we exposed rats to acute 6-h immobilization at the 1 st and 45 th days after cessation of IH. We showed that severity of hypoxic episodes during IH might initiate different adaptive programs. Moderate hypoxia during IH prevents mitochondrial glutathione pool depletion induced by immobilization stress, maintains GSH-redox cycle via activation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, NADP + -dependent isocitrate dehydrogenase, and increases Mn-SOD activity. Such regimen of hypoxic preconditioning caused the decrease of mitochondrial superoxide anion generation as well as of basal and stimulated in vitro lipid peroxidation and this protective effect remained for 45 days under renormoxic conditions. Hypoxic adaptation in a more severe regimen exerted beneficial effects on the mitochondrial antioxidant defense system only at its later phase.

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Section: Introductionmentioning

confidence: 92%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

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“…After rats has been anesthetized with pentobarbital sodium (45 mg/kg ip), hearts were rapidly excised and perfused with Krebs-Henseleit (K-H) solution at 37°C using a Langendorff apparatus at a constant pressure of 80 mmHg as previously described (54). A water-filled latex balloon connected to a pressure transducer (Gould P23Db, AD Instruments, Sydney, NSW, Australia) was inserted into the left ventricular (LV) cavity to achieve a stable LV end-diastolic pressure (LVEDP) of 5-10 mmHg during initial equilibration.…”

Section: Animalmentioning

confidence: 99%

“…To determine whether IHH and MPG affect the irreversible cell injury after I/R, isolated rat hearts subjected to 30 min of ischemia followed by 2 h of reperfusion were frozen, and the LV was cut into 2-mm-thick slices. Sections were then incubated in 1% (wt/vol) triphenyltetrazolium chloride (phosphate buffer, pH 7.4) for 15 min for staining (54). Slices were fixed in 10% formaldehyde to enhance the contrast between stained viable and unstained necrotic tissue.…”

Section: Animalmentioning

confidence: 99%

Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion

Wang

Chen

Zhang

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion. Am J Physiol Heart Circ Physiol 301: H1695-H1705, 2011. First published August 5, 2011; doi:10.1152/ajpheart.00276.2011.-Intermittent hypobaric hypoxia (IHH) protects hearts against ischemiareperfusion (I/R) injury, but the underlying mechanisms are far from clear. ROS are paradoxically regarded as a major cause of myocardial I/R injury and a trigger of cardioprotection. In the present study, we investigated whether the ROS generated during early reperfusion contribute to IHH-induced cardioprotection. Using isolated perfused rat hearts, we found that IHH significantly improved the postischemic recovery of left ventricular (LV) contractile function with a concurrent reduction of lactate dehydrogenase release and myocardial infarct size (20.5 Ϯ 5.3% in IHH vs. 42.1 Ϯ 3.8% in the normoxic control, P Ͻ 0.01) after I/R. Meanwhile, IHH enhanced the production of protein carbonyls and malondialdehyde, respective products of protein oxidation and lipid peroxidation, in the reperfused myocardium and ROS generation in reperfused cardiomyocytes. Such effects were blocked by the mitochondrial ATP-sensitive K ϩ channel inhibitor 5-hydroxydecanoate. Moreover, the IHH-improved postischemic LV performance, enhanced phosphorylation of PKB (Akt), PKC-ε, and glycogen synthase kinase-3␤, as well as translocation of PKC-ε were not affected by applying H 2O2 (20 mol/l) during early reperfusion but were abolished by the ROS scavengers N-(2-mercaptopropionyl-)glycine (MPG) and manganese (III) tetrakis (1-methyl-4-pyridyl)porphyrin. Furthermore, IHH-reduced lactate dehydrogenase release and infarct size were reversed by MPG. Consistently, inhibition of Akt with wortmannin and PKC-ε with εV1-2 abrogated the IHH-improved postischemic LV performance. These findings suggest that IHHinduced cardioprotection depends on elevated ROS production during early reperfusion.reactive oxygen species; ischemia-reperfusion injury EARLY REPERFUSION during evolving myocardial infarction is essential for saving the myocardium, but lethal reperfusion injury can occur and limit the beneficial effects (49). A number of cardioprotective strategies have been developed to ameliorate or retard the irreversible injury. However, the clinical translation of these strategies has failed to achieve the anticipated results (13, 34). Intermittent hypobaric hypoxia (IHH) has been shown to protect the heart against ischemia-reperfusion (I/R) injury by improving the manifestations including contractile dysfunction (3, 33), arrhythmias (31, 52), and cell death (8,27). Recently, we (48) revealed a therapeutic effect of IHH on permanent coronary artery ligation-induced myocardial infarction by attenuating infarct size, myocardial fibrosis, and apoptosis and improving cardiac performance. Because IHH is a relatively simple intervention with a longer protection duration and fewer adverse effects and may offer profound benefit to patients ...

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“…Repeated episodes of hypobaric hypoxia interspersed with normoxic periods [intermittent hypobaric hypoxia (IH)] have long been used for training pilots, mountaineers, and athletes, and even applied for treatment and prevention of human diseases such as hypertension (Serebrovskaya et al, 2008), ischemic coronary artery diseases (Zhu et al, 2006), Parkinson's disease (Lin et al, 2002), and acute myeloid leukemia (Liu et al, 2006). Recently, it has been shown that hypoxia promoted neurogenesis in vitro (Shingo et al, 2001;Jin et al, 2002) and enhanced the proliferation of neuroprogenitor cells (NPCs) in vivo (Zhu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

Zhu¹,

Yan²,

Zhang³

et al. 2010

J. Neurosci.

188

137

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Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressantlike effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.

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Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury

Cited by 63 publications

References 33 publications

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

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