Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

Chen, Tsung-I; Lai, Chun–Kit; Hsieh, Chien-Ju; Tsai, Ke-Li; Yang, Kun‐Ta

doi:10.1007/s11325-010-0448-y

Cited by 14 publications

(18 citation statements)

References 47 publications

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“…In our study, IH raised myocardial levels of the inflammatory markers IL-6, TNF-α, MCP-1, and VCAM, similar to findings of previous studies [10, 58, 59]. Also, similar to previous studies [5, 8, 29], our study found that IH elevated levels of TBARTS and protein carbonyl, suggesting inflammation was accompanied by oxidative stress. These results suggest that IH-induced oxidative stress leads to increased myocardial inflammation.…”

Section: Discussionsupporting

confidence: 92%

“…The IH process has previously been described [28, 29]. In brief, rats were housed in Plexiglas cylindrical chambers (length: 28 cm; diameter: 10 cm; volume: 2.4 L) with snug-fitting lids.…”

Section: Methodsmentioning

confidence: 99%

“…This protocol was adapted and modified from our previous studies [29, 33]. Total cytosolic fraction extracts were obtained from the LV myocardium using a commercially available isolation kit (Pierce, Rockford, IL, USA), according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

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Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Chen

2016

PLoS ONE

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In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

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Section: Discussionsupporting

confidence: 92%

“…The IH process has previously been described [28, 29]. In brief, rats were housed in Plexiglas cylindrical chambers (length: 28 cm; diameter: 10 cm; volume: 2.4 L) with snug-fitting lids.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Chen

2016

PLoS ONE

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“…IH is characterized as cyclic episodes of hypoxia of short duration followed by normoxia [4], leading to increased generation of intracellular reactive oxygen species (ROS) during re-oxygenation following hypoxia [5]. Previously, excess ROS accumulation was itself considered injurious because it can cause lipid peroxidation, protein oxidation, DNA damage [6] and intracellular ion deregulation [7], damaging cellular physiological function.…”

Section: Introductionmentioning

confidence: 99%

Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca²⁺Handling in Neonatal Rat Cardiomyocytes

Chen

Hsu

Lien

et al. 2014

Cell Physiol Biochem

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Background/Aims: Intermittent hypoxia (IH) may exert pre-conditioning-like cardioprotective effects and alter Ca²⁺ regulation; however, the exact mechanism of these effects remains unclear. Thus, we examined Ca²⁺-handling mechanisms induced by IH in rat neonatal cardiomyocytes. Methods: Cardiomyocytes were exposed to repetitive hypoxia-re-oxygenation cycles for 1-4 days. Mitochondrial reactive oxygen species (ROS) generation was determined by flow cytometry, and intracellular Ca²⁺ concentrations were measured using a live-cell fluorescence imaging system. Protein kinase C (PKC) isoforms and Ca²⁺-handling proteins were analysed using immunofluorescence and western blotting. Results: After IH exposure for 4 days, the rate of Ca²⁺ extrusion from the cytosol to the extracellular milieu during 40-mM KCl-induced Ca²⁺ mobilization increased significantly, whereas ROS levels increased mildly. IH activated PKC isoforms, which translocated to the membrane from the cytosol, and Na⁺/Ca²⁺ exchanger-1, leading to enhanced Ca²⁺ efflux capacity. Simultaneously, IH increased sarcoplasmic reticulum (SR) Ca²⁺-ATPase and ryanodine receptor 2 (RyR-2) activities and RyR-2 expression, resulting in improved Ca²⁺ uptake and release capacity of SR in cardiomyocytes. Conclusions: IH-induced mild elevations in ROS generation can enhance Ca²⁺ efflux from the cytosol to the extracellular milieu and Ca²⁺-mediated SR regulation in cardiomyocytes, resulting in enhanced Ca²⁺-handling ability.

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“…IH is associated with increased intracellular reactive oxygen species (ROS) generation during the reoxygenation phase [2]. IH has been reported to result in partially irreversible memory and learning impairments in both animals and humans [3].…”

Section: Introductionmentioning

confidence: 99%

Intermittent hypoxia-induced protein phosphatase 2A activation reduces PC12 cell proliferation and differentiation

et al. 2014

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BackgroundIntermittent hypoxia (IH) plays a critical role in sleep breathing disorder-associated hippocampus impairments, including neurocognitive deficits, irreversible memory and learning impairments. IH-induced neuronal injury in the hippocampus may result from reduced precursor cell proliferation and the relative numbers of postmitotic differentiated neurons. However, the mechanisms underlying IH-induced reactive oxygen species (ROS) generation effects on cell proliferation and neuronal differentiation remain largely unknown.ResultsROS generation significantly increased after 1–4 days of IH without increased pheochromocytoma-12 (PC12) cell death, which resulted in increased protein phosphatase 2A (PP2A) mRNA and protein levels. After 3–4 days of IH, extracellular signal-regulated kinases 1/2 (ERK1/2) protein phosphorylation decreased, which could be reversed by superoxide dismutase (SOD), 1,10-phenanthroline (Phe), the PP2A phosphorylation inhibitors, okadaic acid (OKA) and cantharidin, and the ERK phosphorylation activator nicotine (p < 0.05). In particular, the significantly reduced cell proliferation and increased proportions of cells in the G0/G1 phase after 1–4 days of IH (p < 0.05), which resulted in decreased numbers of PC12 cells, could be reversed by treatment with SOD, Phe, PP2A inhibitors and an ERK activator. In addition, the numbers of nerve growth factor (NGF)-induced PC12 cells with neurite outgrowths after 3–4 days of IH were less than those after 4 days of RA, which was also reversed by SOD, Phe, PP2A inhibitors and an ERK activator.ConclusionsOur results suggest that IH-induced ROS generation increases PP2A activation and subsequently downregulates ERK1/2 activation, which results in inhibition of PC12 cell proliferation through G0/G1 phase arrest and NGF-induced neuronal differentiation.

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Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

Abstract: CIH causes cardiomyocyte loss in SHR mainly through cardiomyocyte necrosis. In WKY however, CIH simultaneously induces apoptosis and necrosis of cardiomyocytes.

Cited by 14 publications

References 47 publications

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca²⁺Handling in Neonatal Rat Cardiomyocytes

Intermittent hypoxia-induced protein phosphatase 2A activation reduces PC12 cell proliferation and differentiation

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Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

Abstract: CIH causes cardiomyocyte loss in SHR mainly through cardiomyocyte necrosis. In WKY however, CIH simultaneously induces apoptosis and necrosis of cardiomyocytes.

Cited by 14 publications

References 47 publications

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca2+Handling in Neonatal Rat Cardiomyocytes

Intermittent hypoxia-induced protein phosphatase 2A activation reduces PC12 cell proliferation and differentiation

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Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca²⁺Handling in Neonatal Rat Cardiomyocytes