nach oben

Erschienen in:

Open Access 15.02.2019 | Sleep Apnea

Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

verfasst von: Lu Bai, Chunying Sun, Huifen Zhai, Chen Chen, Xiaotian Hu, Xiulin Ye, Min Li, Yan Fang, Weimin Yang, Haoyan Wang, Shibo Sun

Erschienen in: Lung | Ausgabe 2/2019

Abstract

Background

Obstructive sleep apnea (OSA) is a disease seriously threatening individual health, which results in serious complications such as hypertension and stroke. These complications are associated with oxidative stress triggered by intermittent hypoxia in OSA. Sestrin2 is a crucial factor involved in oxidative stress. The goal of this study was to investigate if a relationship exists between OSA and Sestrin2.

Methods

We prospectively enrolled 71 subjects, and 16 patients of them with severe OSA completed 4 weeks of nasal continuous positive airway pressure (nCPAP) therapy. We measured and compared the concentration of Sestrin2 in the urine of all subjects, as well as the changes between before and after nCPAP treatment. Additionally, the correlation between Sestrin2 and sleep parameters was analyzed, and the multiple linear regression analysis with stepwise selection was performed to explore the relationship between Sestrin2 and various factors.

Results

A total of 71 subjects were enrolled and divided into two groups: OSA group (n = 41), control group (n = 30). The level of urinary Sestrin2 in OSA patients was significantly higher than that of the control group, and increased with the severity of OSA, while it reduced after nCPAP treatment. Additionally, Sestrin2 was positively correlated with apnea/hypopnea index (AHI), oxygen desaturation index, oxygen saturation < 90% percentage of recording time spent (PRTS) and high-density lipoprotein (HDL), while negatively correlated with the lowest oxygen saturation. Importantly, Sestrin2 was independently associated with AHI, oxygen saturation < 90% PRTS and HDL.

Conclusions

Urinary Sestrin2 is involved in OSA, and is a paramount marker of OSA severity.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Introduction

Obstructive sleep apnea (OSA) is a shared sleep-related disorder. According to the survey, the estimated prevalence of OSA is 0.7–3.3% [1‐3]. It is characterized by periodic recurrent episodes of upper airway obstruction during sleep, resulting in apnea [4], and the occurrence of OSA is capable of disrupting sleep integrity, impairing ventilation, and resulting in intermittent hypoxia [5], which seriously lead to coronary artery disease, high blood pressure, cerebrovascular accident, stroke, etc. [6]. There is increasing evidence that these complications are closely related to oxidative stress triggered by intermittent hypoxia [6‐9].

Sestrin, originally discovered as p53-inducible proteins, is a highly conserved family of proteins that are thought to protect cells from various damages [10]. The Sestrin family has three distinct members in mammals, which include Sestrin1, Sestrin2, and Sestrin3 [11]. Sestrin2, among the three members, also known as hypoxia-inducible gene (Hi95), is an acute response protein that plays a paramount role in various conditions such as excessive oxidative stress, hypoxia, DNA damage, etc. [12]. Moreover, Sestrin2 expression is obviously up-regulated in oxidative stress-related diseases, exerting anti-oxidation, preventing the production of reactive oxygen species (ROS), reducing the accumulation of ROS as an inducible factor of oxidation, and thus protecting cells from oxidative stress [13, 14]. Chronic intermittent hypoxia (CIH) occurs in patients with OSA during sleeping [15], leading to a strong oxidative stress response [16]. Accordingly, we speculated that Sestrin2 might be involved in the OSA. To study the relationship between Sestrin2 and OSA may be beneficial in discovering the reasons of oxidative stress-related complications in OSA patients. However, so far, we have not found any relevant reports. The goal of this study was to investigate the changes in urinary Sestrin2 concentration in OSA patients.

Method

Research Population

We prospectively enrolled 71 subjects who were entirely performed by polysomnography (PSG) tests because of snoring, including 41 newly diagnosed OSA patients and 30 healthy controls at the First Affiliated Hospital of Kunming Medical University, from June 2016 to June 2018. The inclusion criteria were patients with 18–65 years old, and the exclusion criteria were patients with heart failure, lung disease, cerebrovascular disease, kidney disease, metabolic diseases like diabetes, and the OSA patients who have been treated before this study.

All patients underwent a systematic physical examination prior to PSG testing to measure the height, weight, waist-to-hip ratio, and neck circumference (NC). Their body mass index (BMI) was calculated. The Epworth Sleepiness Score (ESS) was used to assess the degree of daytime sleepiness. This study was approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University, and the patient’s informed consents were obtained.

PSG

All subjects were examined by overnight PSG (Alice 5, American) and recorded parameters including EEG, ECG, oral and nasal airflow, oxygen saturation, and chest and abdomen movements. Apnea was defined as a respiratory amplitude reduction ≥ 90% for more than 10 s. Hypopnea was defined as a decrease in respiratory airflow amplitude reduction ≥ 30% with a decrease in oxygen saturation ≥ 3% or arousal [17]. All PSG records were analyzed by two experts to obtain apnea/hypopnea index (AHI). Normal subject was defined with AHI < 5, OSA was defined with AHI ≥ 5. The hypoxemia index was indicated by oxygen saturation < 90% percentage of recording time spent (PRTS).

Pressure Titration Under PSG

An overnight pressure titration was performed under PSG testing using an auto-continuous positive airway pressure (Auto-CPAP) machine (Philips-Respironics REMstarAuto). The airflow signal was collected by the mask pressure signal. The humidifier was routinely used during titration. If the PSG result demonstrated AHI ≤ 5/h, 90th percentile recording pressure was defined as the titration pressure.

nCPAP Treatment

Patients enrolled in the treatment response analysis were treated with a nasal CPAP (nCPAP) machine (Resmed, S9 Escape, Australia). There was a data card on each machine to record the application time. We read the data card and downloaded the data after 4 weeks of treatment. Patients who were treated for more than 4 h/day were included in the treatment analysis.

Urine Test

5–7 mL urine specimens were collected from the patients on an empty stomach in the morning after the PSG test and 4 weeks nCPAP treatment, then centrifugated 20 min by 3000 rpm at 4 °C. Urine supernatant was extracted and stored in − 80 °C refrigerator for testing. The urinary Sestrin2 concentration was measured with an ELISA kit (Mlbio, Shanghai, China). Other tests including fasting blood glucose, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and urine creatinine were tested by the First Affiliated Hospital of Kunming Medical University. Sestrin2 was adjusted with creatinine: adjust Sestrin2 = (Sestrin2/creatinine) × 10⁴.

Statistical Analysis

Data were presented as mean ± standard derivation. In addition, the single-sample Kolmogorov–Smirnov method was used to detect whether the data were normally distributed. Normally distributed data were compared by an unpaired t-test, and the data between before and after treatment were compared with paired t-test. Rank sum test was used for non-normally distributed data. Pearson’s correlation analysis was applied for correlation analysis. Linear stepwise regression analysis was used to detect the relationship between Sestrin2 and other factors (age, gender, waist-to-hip, BMI, NC, AHI, mean oxygen saturation, lowest oxygen saturation, oxygen saturation < 90% PRTS, ESS, TG, TC, LDL, HDL, fasting blood glucose).

Result

71 Subjects were prospectively enrolled in this study, and were divided into two groups: OSA group (39.29 ± 7.73 years old, n = 41) and control group (38.70 ± 8.86 years old, n = 30). All patient characteristics and the results of urinary Sestrin2 were listed in Table 1. OSA patients were divided into three subgroups according to AHI: mild group 5 ≤ AHI < 15, moderate group 15 ≤ AHI < 30, and severe group AHI ≥ 30. Sixteen patients with severe OSA completed 4 weeks nCPAP treatment, and the treatment time was greater than 4 h/day, and then the levels of urinary Sestrin2 after treatment were measured.

Table 1

Demographics, sleep profiles, blood and urinary measurements of the OSA and control groups

	Control group (n = 30)	OSA group (n = 41)	P values
Age (years)	38.70 ± 8.86	39.29 ± 7.73	0.765
Gender (male/female)^a	20/10	32/9	0.416
BMI (kg/m²)	27.09 ± 4.22	28.55 ± 4.62	0.176
Neck circumference (cm)	36.06 ± 5.47	38.56 ± 6.90	0.093
Waist-to-hip ratio	0.88 ± 0.07	0.92 ± 0.08	0.022*
AHI (events/h)	2.32 ± 1.20	35.00 ± 20.86	< 0.001*
ODI (events/h)	1.59 ± 0.90	31.17 ± 19.31	< 0.001*
Lowest oxygen saturation (%)	90.48 ± 0.99	79.93 ± 8.28	< 0.001*
Mean oxygen saturation (%)	93.50 ± 0.94	90.40 ± 2.91	< 0.001*
Oxygen saturation < 90% PRTS (%)	0.46 ± 1.42	19.35 ± 8.92	< 0.001*
Total sleep time (min)	316.8 ± 38.71	329.83 ± 40.71	0.179
Arousal index (events/h)	13.17 ± 7.32	35.86 ± 20.63	< 0.001*
Stage of REM (%)	13.15 ± 3.79	11.36 ± 3.25	0.035*
Stage of NREM (%)	86.85 ± 3.79	88.64 ± 3.25	0.035*
Triglycerides (mmol/L)	1.51 ± 0.61	1.77 ± 1.12	0.224
Sestrin2 (ng/mL creatinine)	2.69 ± 1.11	3.39 ± 1.65	0.035*
Total cholesterol (mmol/L)	4.08 ± 0.80	4.31 ± 0.64	0.180
Low-density lipoprotein (mmol/L)	2.31 ± 0.63	2.51 ± 0.58	0.160
High-density lipoprotein (mmol/L)	1.03 ± 0.29	0.99 ± 0.24	0.532
Fasting blood glucose (mmol/L)	4.31 ± 0.53	4.56 ± 0.56	0.064
ESS (scores)	6.73 ± 2.46	11.92 ± 4.30	< 0.001*

Values are indicated as the mean ± standard deviation

BMI body mass index, AHI apnea/hypopnea index, ODI oxygen desaturation index, PRTS percentage of recording time spent, REM rapid eye movement, NREM non-rapid eye movement, ESS Epworth Sleepiness Score

*P < 0.05, the results are statistically significant

^aValues are indicated as numbers

The level of urinary Sestrin2 in the OSA group was significantly higher than that of the control group (P = 0.035), and as the severity of OSA increased, Sestrin2 level also increased. In addition, Sestrin2 was significantly reduced after nCPAP treatment (Fig. 1). Subgroup analysis demonstrated that the concentration of Sestrin2 in the severe OSA group was significantly higher than that of the other subgroups and control group (Fig. 2).

Sestrin2 was positively correlated with AHI, oxygen desaturation index (ODI), oxygen saturation < 90% PRTS, HDL, fasting blood glucose, and OSA severity, but negatively correlated with lowest oxygen saturation. Importantly, these relationships still existed after adjusting for age, gender, waist-to-hip, NC, and BMI (Table 2).

Table 2

Spearman’s correlations between adjusted Sestrin2 and the other factors

	r	P values	r ^a	P values
Age	0.170	0.156
BMI	0.075	0.535
Neck circumference	−0.043	0.725
Waist-to-hip ratio	0.073	0.545
AHI	0.376	0.001*	0.566	< 0.001*
ODI	0.314	0.008*	0.559	< 0.001*
Lowest oxygen saturation	−0.358	0.002*	−0.350	0.004*
Mean oxygen saturation	−0.160	0.183	−0.138	0.268
Oxygen saturation < 90% PRTS	0.378	0.001*	0.562	< 0.001*
Total sleep time	−0.047	0.698	0.044	0.726
Arousal index	−0.003	0.979	0.215	0.083
Stage of REM	0.070	0.564	−0.016	0.901
Stage of NREM	−0.070	0.564	0.016	0.901
Triglycerides	−0.054	0.654	−0.030	0.814
Total cholesterol	0.029	0.811	0.084	0.505
Low-density lipoprotein	0.001	0.996	−0.012	0.922
High-density lipoprotein	0.344	0.003*	0.325	0.008*
Fasting blood glucose	0.305	0.010*	0.274	0.026*
Epworth Sleepiness Score	0.298	0.011*	0.259	0.036*
Severity of OSA	0.405	0.000*	0.388	0.001*

BMI body mass index, AHI apnea/hypopnea index, ODI oxygen desaturation index, PRTS percentage of recording time spent, REM rapid eye movement, NREM non-rapid eye movement, OSA obstructive sleep apnea

*P < 0.05, the results are statistically significant

^aAdjusting for age, BMI, gender, waist-to-hip ratio, neck circumference

The multiple linear regression analysis with stepwise selection showed that Sestrin2 was associated with AHI, oxygen saturation < 90% PRTS, and HDL (Table 3). However, there was no association between Sestrin2 and waist-to-hip ratio.

Table 3

Stepwise multiple regression model of adjusted urinary Sestrin2 levels in the OSA group (adjusted R² = 0.745)

	B (SE)	β	P values
Constant	−1.078 (0.525)		0.047*
AHI	0.033 (0.007)	0.420	< 0.001*
Oxygen saturation < 90% PRTS	0.094 (0.016)	0.509	< 0.001*
HDL	1.435 (0.444)	0.262	0.003*

Independent variables considered: age, gender, BMI, waist-to-hip ratio, neck circumference, AHI, lowest oxygen saturation, oxygen saturation < 90% PRTS, total sleep time, stage of rapid eye movement sleep, Epworth Sleepiness Score, triglycerides, total cholesterol, low-density lipoprotein, HDL, fasting blood glucose

AHI apnea/hypopnea index, PRTS percentage of recording time spent, HDL high-density lipoprotein

*P < 0.05, the results are statistically significant

Discussion

This study was the first report on investigation of Sestrin2 in OSA, and the results showed that the Sestrin2 level elevated in OSA and decreased after nCPAP treatment. In addition, Sestrin2 was positively correlated with AHI, ODI, and oxygen saturation < 90% PRTS. Most importantly, the multiple regression analysis demonstrated that Sestrin2 was associated with AHI and oxygen saturation < 90% PRTS. It suggested that Sestrin2 played an important role in OSA.

Several authors [12, 13, 18‐20] suggested that hypoxia, stress, or inflammation led to a growth of directed autophagy of Kelch-like ECH-associated protein 1 (Keap1), thereby decomposed the key regulator of oxidative genes, nuclear erythroid-related factor 2 (Nrf2). The production and accumulation of ROS inhibited by Nrf2 will lead to an increase in Sestrin2 [21, 22]. Moreover, hypoxia, stress, or inflammation will activate the mTORC1. Sestrin2, as a leucine sensor, is significantly increased in mTORC1 activation [23‐25]. It was reported that hypoxia, oxidative stress, and inflammation recurred in OSA [26‐28]. In present study, Sestrin2 was positively correlated with ODI and oxygen saturation < 90% PRTS. In addition, the multiple regression analysis showed that Sestrin2 was associated with oxygen saturation < 90% PRTS. Therefore, the increasing of urinary Sestrin2 might be triggered by intermittent hypoxia in OSA.

It was reported that Sestrin2 was a conserved antioxidant protein, and could be activated under pressure to protect cells from oxidative stress [29]. Essler et al. [30] suggested that Sestrin2 upregulation mediated by hypoxia was beneficial to counteracting the production of ROS, and ROS frequently accumulated and increased due to CIH in OSA [4]. Consequently, Sestrin2 might play an advantageous role in anti-oxidative stress in OSA.

It was reported that nCPAP could significantly reduce ODI and oxygen saturation < 90% PRTS in patients with OSA, and improve the hypoxia of OSA during sleep [31, 32]. In addition, the nCPAP could improve the oxidative stress and inflammatory response [32, 33]. In this study, the Sestrin2 reduced with the nCPAP treatment. Hypoxia, which might result in the elevation of Sestrin2, relieved after nCPAP treatment, thus the Sestrin2 decreased.

It was reported that central adiposity was associated with OSA [34], and it could predict the onset of OSA [35]. In present study, there was no relationship between waist-to-hip ratio and Sestrin2, which meant that the central adiposity had no effect on the change of Sestrin2.

Moreover, sleep architecture impairment of OSA might affect some factors, such as TNF-α [36]. However, in this study, Sestrin2 was not related to REM, NREM sleep, arousal index, and total sleep time, which meant that sleep architecture impairment of OSA did not contribute to increasing Sestrin2 level.

It was reported that there was a significant positive correlation between Sestrin2 and HDL [37]. The HDL played an antioxidant role [38], and the HDL levels were positively correlated with obesity status [39, 40]. Moreover, Sestrin2 regulated the PERK-c/EBPβ pathway by mediating mTORCI [41, 42], and inhibited the ROS-mediated p38 MAPK activation and interfered the expression of uncoupling protein 1 (Ucp1), subsequently resulting in the decrease of heat production and the increase of adipose tissue, which led to obesity [43, 44]. In addition, HDL was reduced in inflammatory conditions [45], while Sestrin2 could inhibit TLR-mediated inflammatory responses in macrophages [46]. Accordingly, it might be the obesity and inflammation that caused the association between Sestrin2 and HDL in this study.

However, there was a main limitation that the present study was not randomized; Small sample size was also a limitation. In addition, another limitation was that we used Auto-CPAP titration under PSG for pressure titration instead of the standard CPAP titration, though it was suggested that Auto-CPAP titration under PSG was also effective.

Conclusion

Urinary Sestrin2 is involved in OSA, and is closely related to the severity of OSA. It decreases with nCPAP treatment. Accordingly, urinary Sestrin2 is a paramount marker of OSA severity.

Acknowledgements

None.

Compliance with Ethical Standards

Conflict of interest

None.

Ethical Approval

All procedures performed in studies involving human participants were consistent with the Ethical Standards of the Institutional and/or Nation Research Committee, as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt testen ¹

e.Med Innere Medizin

Kombi-Abonnement

Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.

Jetzt testen ²

e.Med Allgemeinmedizin

Kombi-Abonnement

Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.

Jetzt testen ³

Lavie P (2002) Incidence of sleep apnea in a presumably healthy working population: a significant relationship with excessive daytime sleepiness. Sleep 25:312–318CrossRefPubMed

Gislason T, Almqvist M, Eriksson G et al (1988) Prevalence of sleep apnea syndrome among Swedish men—an epidemiological study. J Clin Epidemiol 41:571–576CrossRefPubMed

Bixler EO, Vgontzas AN, Ten Have T et al (1998) Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med 157:144–148. https://doi.org/10.1164/ajrccm.157.1.9706079 CrossRefPubMed

Bouloukaki I, Mermigkis C, Kallergis EM et al (2015) Obstructive sleep apnea syndrome and cardiovascular disease: the influence of C-reactive protein. World J Exp Med 5:77–83. https://doi.org/10.5493/wjem.v5.i2.77 CrossRefPubMedPubMedCentral

Elsharkawi I, Gozal D, Macklin EA et al (2017) Urinary biomarkers and obstructive sleep apnea in patients with Down syndrome. Sleep Med 34:84–89. https://doi.org/10.1016/j.sleep.2017.02.005 CrossRefPubMedPubMedCentral

Franklin KA, Lindberg E (2015) Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea. J Thorac Dis 7:1311–1322. https://doi.org/10.3978/j.issn.2072-1439.2015.06.11 CrossRefPubMedPubMedCentral

Flora SJ (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2:191–206. https://doi.org/10.4161/oxim.2.4.9112 CrossRefPubMedPubMedCentral

Dalle-Donne I, Rossi R, Colombo R et al (2006) Biomarkers of oxidative damage in human disease. Clin Chem 52:601–623. https://doi.org/10.1373/clinchem.2005.061408 CrossRefPubMed

Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. https://doi.org/10.1038/35041687 CrossRef

10.

Donahoe SM, Stewart GC, McCabe CH et al (2007) Diabetes and mortality following acute coronary syndromes. JAMA 298:765–775. https://doi.org/10.1001/jama.298.7.765 CrossRefPubMed

11.

Budanov AV, Shoshani T, Faerman A et al (2002) Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 21:6017–6031. https://doi.org/10.1038/sj.onc.1205877 CrossRefPubMed

12.

Lee JH, Budanov AV, Karin M (2013) Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 18:792–801. https://doi.org/10.1016/j.cmet.2013.08.018 CrossRefPubMed

13.

Chuang YC, Yang JL, Yang DI et al (2015) Roles of Sestrin2 and ribosomal protein S6 in transient global ischemia-induced hippocampal neuronal injury. Int J Mol Sci 16:26406–26416. https://doi.org/10.3390/ijms161125963 CrossRefPubMedPubMedCentral

14.

Rai N, Kumar R, Desai GR et al (2016) Relative alterations in blood-based levels of Sestrin in Alzheimer’s disease and mild cognitive impairment patients. J Alzheimers Dis 54:1147–1155. https://doi.org/10.3233/JAD-160479 CrossRefPubMed

15.

Zhou L, Chen P, Peng Y et al (2016) Role of oxidative stress in the neurocognitive dysfunction of obstructive sleep apnea syndrome. Oxid Med Cell Longev 2016:9626831PubMedPubMedCentral

16.

Eisele HJ, Markart P, Schulz R (2015) Obstructive sleep apnea, oxidative stress, and cardiovascular disease: evidence from human studies. Oxid Med Cell Longev 2015:608438. https://doi.org/10.1155/2015/608438 CrossRefPubMedPubMedCentral

17.

Dumitrascu R, Heitmann J, Seeger W et al (2013) Obstructive sleep apnea, oxidative stress and cardiovascular disease: lessons from animal studies. Oxid Med Cell Longev 2013:234631. https://doi.org/10.1155/2013/234631 CrossRefPubMedPubMedCentral

18.

The Report of an American Academy of Sleep Medicine Task Force (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22:667–689CrossRef

19.

Li K, Chen Z, Qin Y et al (2018) MiR-664a-3p expression in patients with obstructive sleep apnea: a potential marker of atherosclerosis. Medicine (Baltim) 97:e9813. https://doi.org/10.1097/MD.0000000000009813 CrossRef

20.

Ye J, Wang M, Xu Y et al (2017) Sestrins increase in patients with coronary artery disease and associate with the severity of coronary stenosis. Clin Chim Acta 472:51–57. https://doi.org/10.1016/j.cca.2017.07.020 CrossRefPubMed

21.

Fu H, Song W, Wang Y et al (2018) Radiosensitizing effects of Sestrin2 in PC3 prostate cancer cells. Iran J Basic Med Sci 21:621–624. https://doi.org/10.22038/IJBMS.2018.18283.4923 CrossRefPubMedPubMedCentral

22.

Bae SH, Sung SH, Oh SY et al (2013) Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab 17:73–84. https://doi.org/10.1016/j.cmet.2012.12.002 CrossRefPubMed

23.

Zeng N, D’Souza RF, Sorrenson B et al (2018) The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle. Eur J Appl Physiol 118:1241–1253. https://doi.org/10.1007/s00421-018-3853-8 CrossRefPubMed

24.

Lee M, Kim JH, Yoon I et al (2018) Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway. Proc Natl Acad Sci USA 115:E5279–E5288. https://doi.org/10.1073/pnas.1801287115 CrossRefPubMed

25.

Wolfson RL, Sabatini DM (2017) The dawn of the age of amino acid sensors for the mTORC1 pathway. Cell Metab 26:301–309. https://doi.org/10.1016/j.cmet.2017.07.001 CrossRefPubMedPubMedCentral

26.

Tóthová L, Hodosy J, Mucska I et al (2014) Salivary markers of oxidative stress in patients with obstructive sleep apnea treated with continuous positive airway pressure. Sleep Breath 18:563–570. https://doi.org/10.1007/s11325-013-0919-z CrossRefPubMed

27.

Malhotra A, White DP (2002) Obstructive sleep apnoea. Lancet 360:237–245. https://doi.org/10.1016/S0140-6736(02)09464-3 CrossRefPubMed

28.

Edwards KM, Tomfohr LM, Mills PJ et al (2011) Macrophage migratory inhibitory factor (MIF) may be a key factor in inflammation in obstructive sleep apnea. Sleep 34:161–163CrossRefPubMedPubMedCentral

29.

Zhang LL, Zhang ZJ (2018) Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2. Eur Rev Med Pharmacol Sci 22:3493–3501. https://doi.org/10.26355/eurrev_201806_15176 CrossRefPubMed

30.

Essler S, Dehne N, Brune B (2009) Role of Sestrin2 in peroxide signaling in macrophages. FEBS Lett 583:3531–3535. https://doi.org/10.1016/j.febslet.2009.10.017 CrossRefPubMed

31.

Zhang J, Tan H, Shi XN et al (2006) The effect of nasal continuous positive airway pressure on endothelial function in obstructive sleep apnea–hypopnea syndrome with coronary heart disease. Zhonghua Nei Ke Za Zhi 45:188–191PubMed

32.

Christou K, Kostikas K, Pastaka C et al (2009) Nasal continuous positive airway pressure treatment reduces systemic oxidative stress in patients with severe obstructive sleep apnea syndrome. Sleep Med 10:87–94. https://doi.org/10.1016/j.sleep.2007.10.011 CrossRefPubMed

33.

Schulz R, Mahmoudi S, Hattar K et al (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570. https://doi.org/10.1164/ajrccm.162.2.9908091 CrossRefPubMed

34.

Schäfer H, Pauleit D, Sudhop T et al (2002) Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest 122:829–839CrossRefPubMed

35.

Gaines J, Vgontzas AN, Fernandez-Mendoza J et al (2016) Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents. Am J Physiol Endocrinol Metab 311:E851–E858. https://doi.org/10.1152/ajpendo.00249.2016 CrossRefPubMedPubMedCentral

36.

Hirotsu C, Albuquerque RG, Nogueira H et al (2017) The relationship between sleep apnea, metabolic dysfunction and inflammation: the gender influence. Brain Behav Immun 59:211–218. https://doi.org/10.1016/j.bbi.2016.09.005 CrossRefPubMed

37.

Nourbakhsh M, Sharifi R, Ghorbanhosseini SS (2017) Evaluation of plasma TRB3 and Sestrin-2 levels in obese and normal-weight children. Child Obes 13:409–414. https://doi.org/10.1089/chi.2017.0082 CrossRefPubMed

38.

Kotani K, Tsuzaki K, Taniguchi N et al (2013) Correlation between reactive oxygen metabolites and atherosclerotic risk factors in patients with type diabetes mellitus. Indian J Med Res 137:742–748PubMedPubMedCentral

39.

Nigro E, Scudiero O, Monaco ML et al (2014) New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int 2014:658913. https://doi.org/10.1155/2014/658913 CrossRefPubMedPubMedCentral

40.

Christou GA, Kiortsis DN (2013) Adiponectin and lipoprotein metabolism. Obes Rev 14:939–949. https://doi.org/10.1111/obr.12064 CrossRefPubMed

41.

Soontornniyomkij V, Soontornniyomkij B, Moore DJ et al (2012) Antioxidant sestrin-2 redistribution to neuronal soma in human immunodeficiency virus-associated neurocognitive disorders. J Neuroimmune Pharmacol 7:579–590. https://doi.org/10.1007/s11481-012-9357-0 CrossRefPubMedPubMedCentral

42.

Park HW, Park H, Ro SH et al (2014) Hepatoprotective role of Sestrin2 against chronic ER stress. Nat Commun 5:4233. https://doi.org/10.1038/ncomms5233 CrossRefPubMedPubMedCentral

43.

Kotani K, Fujiwara S, Tsuzaki K et al (2011) The association between the uncoupling protein-1 gene A-3826G polymorphism and high-density lipoprotein cholesterol in a general japanese population: a consideration of the obesity status. J Clin Med Res 3:319–324. https://doi.org/10.4021/jocmr738w CrossRefPubMedPubMedCentral

44.

Ro SH, Nam M, Jang I et al (2014) Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species. Proc Natl Acad Sci USA 111:7849–7854. https://doi.org/10.1073/pnas.1401787111 CrossRefPubMed

45.

Barter P (2002) Effects of inflammation on high-density lipoproteins. Arterioscler Thromb Vasc Biol 22:1062–1063CrossRefPubMed

46.

Yang JH, Kim KM, Kim MG et al (2015) Role of sestrin2 in the regulation of proinflammatory signaling in macrophages. Free Radic Biol Med 78:156–167. https://doi.org/10.1016/j.freeradbiomed.2014.11.002 CrossRefPubMed

Titel: Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea
verfasst von: Lu Bai
Chunying Sun
Huifen Zhai
Chen Chen
Xiaotian Hu
Xiulin Ye
Min Li
Yan Fang
Weimin Yang
Haoyan Wang
Shibo Sun
Publikationsdatum: 15.02.2019
Verlag: Springer US
Erschienen in: Lung / Ausgabe 2/2019
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-019-00205-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

23.04.2024 | Prävention und Rehabilitation in der Kardiologie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

Abstract

Background

Methods

Results

Conclusions

Publisher’s Note

Introduction

Method

Research Population

PSG

Pressure Titration Under PSG

nCPAP Treatment

Urine Test

Statistical Analysis

Result

Discussion

Conclusion

Acknowledgements

Compliance with Ethical Standards

Conflict of interest

Ethical Approval

Publisher’s Note

Unsere Produktempfehlungen

e.Med Interdisziplinär

e.Med Innere Medizin

e.Med Allgemeinmedizin

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Publisher’s Note

Introduction

Method

Research Population

PSG

Pressure Titration Under PSG

nCPAP Treatment

Urine Test

Statistical Analysis

Result

Discussion

Conclusion

Acknowledgements

Compliance with Ethical Standards

Conflict of interest

Ethical Approval

Informed Consent

Publisher’s Note

Unsere Produktempfehlungen

e.Med Interdisziplinär

e.Med Innere Medizin

e.Med Allgemeinmedizin

Weitere Artikel der Ausgabe 2/2019

Prognostic Accuracy of Three COPD Classification Systems in Relation to Long-Term Mortality of COPD Patients: A Prospective Multicenter Study

The Role of the Cerebellum in Control of Swallow: Evidence of Inspiratory Activity During Swallow

Inpatient Prevalence, Expenditures, and Comorbidities of Sarcoidosis: Nationwide Inpatient Sample 2013–2014

The Burden of Sarcoidosis Symptoms from a Patient Perspective

Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD

The Inflammatory Effect of Iron Oxide and Silica Particles on Lung Epithelial Cells

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Innere Medizin