学科主题临床医学
C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model
Chou, Yu-Ting1,2,3,4; Zhan, Guanxia5; Zhu, Yan5; Fenik, Polina5; Panossian, Lori5,6; Li, YanPeng5; Zhang, Jing7; Veasey, Sigrid5,6
关键词Hypoxia reoxygenation unfolded protein response PERK GADD153 and gp91(phox)
刊名SLEEP
2013-04-01
DOI10.5665/sleep.2528
36期:4页:481-492
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Clinical Neurology ; Neurosciences
资助者NIH HLBI ; NIH HLBI
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; TERM INTERMITTENT HYPOXIA ; UPPER AIRWAY MUSCLE ; NADPH OXIDASE ; OXIDATIVE STRESS ; CHOLINE-ACETYLTRANSFERASE ; NEURONAL DEATH ; MURINE MODEL ; DISORDERS ; MICE
英文摘要

Study Objectives: Obstructive sleep apnea (OSA) is associated with cognitive impairment and neuronal injury. Long-term exposure to intermittent hypoxia (LTIH) in rodents, modeling the oxygenation patterns in sleep apnea, results in NADPH oxidase 2 (Nox2) oxidative injury to many neuronal populations. Brainstem motoneurons susceptible to LTIH injury show uncompensated endoplasmic reticulum stress responses with increased (CCAAT/enhancer binding protein homologous protein (CHOP). We hypothesized that CHOP underlies LTIH oxidative injury. In this series of studies, we first determined whether CHOP is upregulated in other brain regions susceptible to LTIH oxidative Nox2 injury and then determined whether CHOP plays an adaptive or injurious role in the LTIH response. To integrate these findings with previous studies examining LTIH neural injury, we examined the role of CHOP in Nox2, hypoxia-inducible factor-1 alpha (HIF-1 alpha) responses, oxidative injury and apoptosis, and neuron loss.

Design: Within/between mice subjects.

Setting: Laboratory setting.

Participants/Subjects: CHOP null and wild-type adult male mice.

Interventions: LTIH or sham LTIH.

Measurements and Main Results: Relative to wild-type mice, CHOP-/- mice conferred resistance to oxidative stress (superoxide production/carbonyl proteins) in brain regions examined: cortex, hippocampus, and motor nuclei. CHOP deletion prevented LTIH upregulation of Nox2 and HIF-1 alpha in the hippocampus, cortex, and brainstem motoneurons and protected mice from neuronal apoptosis and motoneuron loss.

Conclusions: Endogenous CHOP is necessary for LTIH-induced HIF-1 alpha, Nox2 upregulation, and oxidative stress; CHOP influences LTIH-induced apoptosis in neurons and loss of neurons. Findings support the concept that minimizing CHOP may provide neuroprotection in OSA.

语种英语
所属项目编号HL079555 ; HL096037
资助者NIH HLBI ; NIH HLBI
WOS记录号WOS:000316939000007
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65803
专题北京大学第一临床医学院_呼吸和危重症医学科
作者单位1.Chang Gung Mem Hosp, Sleep Ctr, Chiayi, Taiwan
2.Chang Gung Mem Hosp, Dept Pulm & Crit Care Med, Chiayi, Taiwan
3.Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan, Taiwan
4.Chang Gung Univ Sci & Technol, Tao Yuan, Taiwan
5.Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
6.Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA
7.Peking Univ, Hosp 1, Dept Pulm Med, Beijing 100871, Peoples R China
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GB/T 7714
Chou, Yu-Ting,Zhan, Guanxia,Zhu, Yan,et al. C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model[J]. SLEEP,2013,36(4):481-492.
APA Chou, Yu-Ting.,Zhan, Guanxia.,Zhu, Yan.,Fenik, Polina.,Panossian, Lori.,...&Veasey, Sigrid.(2013).C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model.SLEEP,36(4),481-492.
MLA Chou, Yu-Ting,et al."C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model".SLEEP 36.4(2013):481-492.
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