Lymphocytes from intermittent hypoxia-exposed rats increase the apoptotic signals in endothelial cells via oxidative and inflammatory injury in vitro

Guo, Hengjuan; Cao, Jie; Li, Jinna; Yang, Xiaoyan; Jiang, Junnan; Feng, Jing; Li, Shuo; Zhang, Jing; Chen, Bao-yuan

doi:10.1007/s11325-015-1128-8

Cited by 11 publications

(12 citation statements)

References 30 publications

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“…Tempol, known as an antioxidant, promotes the clearance of ROS and protects mitochondria from oxidative damage. Previous reports have shown that tempol or other antioxidants can prevent HIF-1α-mediated cancer progression [ 37 , 51 – 53 ]. Consistent with these reports, our findings suggest that antioxidant tempol attenuated melanoma lung metastasis and oxidative stress, as well as decreased HIF-1α expression.…”

Section: Discussionmentioning

confidence: 99%

“…It also exerts neuroprotective effects by reducing superoxide anions and preventing peroxynitrite-associated inflammation [ 34 – 36 ]. Recently, tempol has been confirmed to attenuate apoptotic signals in endothelial cells from IH-exposed rats by decreasing oxidative stress and inflammation injury [ 37 ]. Therefore, it is reasonable to hypothesize that tempol may attenuate IH-induced tumor metastasis by decreasing oxidative stress and inflammation responses.…”

Section: Introductionmentioning

confidence: 99%

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Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Ren

et al. 2018

Respir Res

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BackgroundRecently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated.MethodsC57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment. Then, the animals were randomly distributed into three groups (n = 8 each): normoxia (N) group, IH group, and antioxidant tempol group (IHT, exposed to IH after treatment with tempol). After the mice were sacrificed, the number and weight of lung metastatic colonies were assessed. The lung tissues with tumor metastasis were analyzed for markers of oxidative stress and inflammation and for HIF-1α using western blotting and real-time PCR (qRT-PCR). The level of reactive oxygen species (ROS) in B16F10 cell was also assessed after N, IH and IH with tempol treatments.ResultsCompared with normoxia, IH significantly increased the number and weight of mouse lung metastatic colonies. Treatment of B16F10 cells with IH significantly enhanced ROS generation. Lung tissues with tumor metastasis provided evidence of increased oxidative stress, as assessed by p22phox and SOD mRNA levels and the NRF2 protein level, as well as increased inflammation, as assessed by TNF-α and IL-6 mRNA levels and the NF-κB P65 protein level. HIF-1α protein levels were increased in response to IH treatment. Tempol, an important antioxidant, ameliorated IH-induced melanoma lung metastasis in mice and reduced oxidative stress and inflammation responses.ConclusionsThese results support the hypothesis that oxidative stress and inflammation responses play an important role in the pathogenesis of OSA-like IH-induced melanoma lung metastasis in mice. Antioxidant intervention provides a novel strategy for the prevention and treatment of cancer in OSA populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Ren

et al. 2018

Respir Res

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“… 40 Tempol was also found to attenuate the pro-apoptotic effect of IH-induced lymphocytes on endothelial cells. 26 We also demonstrated a significant decrease in the apoptosis level of endothelial cells and adhesion molecule levels in OS rats treated with tempol. These results may support the potential of tempol as a treatment for OS-induced cardiovascular complications as an alternative to CPAP.…”

Section: Discussionmentioning

confidence: 50%

“…As previously described, 26 we used a gas control delivery system for IH exposure, which regulated flow (5 L/min) of pure nitrogen or clean air continuously into a customized IH housing chamber (23×20×12 cm=5520 cm 3 ≈5.5 L) to maintain designated continuous hypoxia or normoxia environment. Software edited with Visual C++ computer language (Jing Feng, Tianjin Medical University General Hospital Respiratory Simulation System 1.0, Tianjin, China, 2005) was applied to control the duration of hypoxia (first 30 s) or reoxygenation (latter 90 s) phases, producing 30 cycles of alternations per hour.…”

Section: Methodsmentioning

confidence: 99%

Effects of Antioxidant Tempol on Systematic Inflammation and Endothelial Apoptosis in Emphysematous Rats Exposed to Intermittent Hypoxia

Zhao

et al. 2018

Yonsei Med J

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PurposeObstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease (CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however, underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS can lead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the intervention effects of antioxidant tempol.Materials and MethodsMale Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia (IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed in OS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh blood were harvested for analysis of endothelial markers and apoptosis.ResultsThe levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelial cells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group, and were lower in OST group than in OS and OSN groups (all p<0.001).ConclusionSynergistic effects of IH with cigarette smoke-induced emphysema produce a greater inflammatory status and endothelial apoptosis. OS-related inflammation and endothelial cell apoptosis may play important roles in promoting cardiovascular dysfunction, and antioxidant tempol could achieve a partial protective effect.

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“…Then, in turn, the stabilization of HIF-1α promotes the synthesis of ROS in mitochondria to induce cell death via the suppression of AMP-activated protein kinase (100,101). HIF-1α stabilization, along with a decline in Bcl-2 and substantial caspase-3 expression, has been observed after IH exposure (102). Furthermore, a large number of apoptotic events have been identified in rat myocardium exposed to IH (103), and the inhibition of HIF-1α expression has been shown to decrease neuronal apoptosis (104).…”

Section: Ros-induced Consequences Lead To Cognitive Impairment In Slementioning

confidence: 99%

The role of reactive oxygen species in cognitive impairment associated with sleep apnea

Yang

Chen

2020

Exp Ther Med

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Obstructive sleep apnea (OSA), a common breathing and sleeping disorder, is associated with a broad range of neurocognitive difficulties. Intermittent hypoxia (IH), one major characteristic of OSA, has been shown to impair learning and memory due to increased levels of reactive oxygen species (ROS). Under normal conditions, ROS are produced in low concentrations and act as signaling molecules in different processes. However, IH treatment leads to elevated ROS production via multiple pathways, including mitochondrial electron transport chain dysfunction and in particular complex I dysfunction, and induces oxidative tissue damage. Moreover, elevated ROS results in the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) and increased activity of peroxisomes, such as NADPH oxidase, xanthine oxidase and phospholipase A2. Furthermore, oxidative tissue damage has been found in regions of the brains of patients with OSA, including the cortex and hippocampus, which are associated with memory and executive function. Furthermore, increased ROS levels in these regions of the brain induce damage via inflammation, apoptosis, ER stress and neuronal activity disturbance. The present review focuses on the mechanism of excessive ROS production in an OSA model and the relationship between ROS and cognitive impairment. Contents 1. Introduction 2. ROS formation 3. ROS-induced consequences lead to cognitive impairment in sleep apnea 4. Conclusion

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Lymphocytes from intermittent hypoxia-exposed rats increase the apoptotic signals in endothelial cells via oxidative and inflammatory injury in vitro

Abstract: Lymphocytes from intermittent hypoxia-exposed rats increased the apoptotic signals in endothelial cells via oxidative and inflammatory injury in vitro, which could be attenuated by tempol.

Cited by 11 publications

References 30 publications

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Effects of Antioxidant Tempol on Systematic Inflammation and Endothelial Apoptosis in Emphysematous Rats Exposed to Intermittent Hypoxia

The role of reactive oxygen species in cognitive impairment associated with sleep apnea

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