Chronic Intermittent Hypoxia Triggers a Senescence-like Phenotype in Human White Preadipocytes.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
21
03
2019
accepted:
03
04
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
25
11
2020
Statut:
epublish
Résumé
Obstructive sleep apnea (OSA) is a common sleep disorder associated with obesity. Emerging evidence suggest that OSA increases the risk of cardiovascular morbidity and mortality partly via accelerating the process of cellular aging. Thus, we sought to examine the effects of intermittent hypoxia (IH), a hallmark of OSA, on senescence in human white preadipocytes. We demonstrate that chronic IH is associated with an increased generation of mitochondrial reactive oxygen species along with increased prevalence of cells with nuclear localization of γH2AX & p16. A higher prevalence of cells positive for senescence-associated β-galactosidase activity was also evident with chronic IH exposure. Intervention with aspirin, atorvastatin or renin-angiotensin system (RAS) inhibitors effectively attenuated IH-mediated senescence-like phenotype. Importantly, the validity of in vitro findings was confirmed by examination of the subcutaneous abdominal adipose tissue which showed that OSA patients had a significantly higher percentage of cells with nuclear localization of γH2AX & p16 than non-OSA individuals (20.1 ± 10.8% vs. 10.3 ± 2.7%, P
Identifiants
pubmed: 32321999
doi: 10.1038/s41598-020-63761-7
pii: 10.1038/s41598-020-63761-7
pmc: PMC7176724
doi:
Substances chimiques
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
H2AX protein, human
0
Histones
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6846Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL065176
Pays : United States
Références
Somers, V. K. et al. Sleep Apnea and Cardiovascular Disease. Journal of the American College of Cardiology 52, 686 (2008).
pubmed: 18702977
doi: 10.1016/j.jacc.2008.05.002
Peker, Y. et al. Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea. The RICCADSA Randomized Controlled Trial. Am J Respir Crit Care Med 194, 613–620 (2016).
pubmed: 26914592
doi: 10.1164/rccm.201601-0088OC
McEvoy, R. D. et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. New England Journal of Medicine 375, 919–931 (2016).
pubmed: 27571048
doi: 10.1056/NEJMoa1606599
pmcid: 27571048
Barbé, F. et al. Effect of Continuous Positive Airway Pressure on the Incidence of Hypertension and Cardiovascular Events in Nonsleepy Patients With Obstructive Sleep Apnea: A Randomized Controlled Trial. JAMA 307, 2161–2168 (2012).
pubmed: 22618923
doi: 10.1001/jama.2012.4366
pmcid: 22618923
Fyhrquist, F., Saijonmaa, O. & Strandberg, T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol 10, 274–283 (2013).
pubmed: 23478256
doi: 10.1038/nrcardio.2013.30
pmcid: 23478256
Kirkland, J. L. & Tchkonia, T. Cellular Senescence: A Translational Perspective. EBioMedicine 21, 21–28 (2017).
pubmed: 28416161
pmcid: 28416161
doi: 10.1016/j.ebiom.2017.04.013
Kovacic, J. C., Moreno, P., Hachinski, V., Nabel, E. G. & Fuster, V. Cellular Senescence, Vascular Disease, and Aging. Circulation 123, 1650–1660 (2011).
pubmed: 21502583
doi: 10.1161/CIRCULATIONAHA.110.007021
pmcid: 21502583
Rodier, F. & Campisi, J. Four faces of cellular senescence. J Cell Biol 192, 547–556 (2011).
pubmed: 21321098
pmcid: 3044123
doi: 10.1083/jcb.201009094
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123, 966–972 (2013).
pubmed: 23454759
pmcid: 3582125
doi: 10.1172/JCI64098
Berg, A. H. & Scherer, P. E. Adipose tissue, inflammation, and cardiovascular disease. Circ. Res. 96, 939–949 (2005).
pubmed: 15890981
doi: 10.1161/01.RES.0000163635.62927.34
pmcid: 15890981
Muñoz-Espín, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15, 482–496 (2014).
pubmed: 24954210
doi: 10.1038/nrm3823
pmcid: 24954210
Tchkonia, T. et al. Fat tissue, aging, and cellular senescence. Aging Cell 9, 667–684 (2010).
pubmed: 20701600
pmcid: 2941545
doi: 10.1111/j.1474-9726.2010.00608.x
Baker, D. J. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530, 184–189 (2016).
pubmed: 26840489
pmcid: 26840489
doi: 10.1038/nature16932
Justice, J. N. et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EbioMedicine, https://doi.org/10.1016/j.ebiom.2018.12.052 (2019).
Carreras, A. et al. Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice. Sleep 37, 1817–1824 (2014).
pubmed: 25364077
pmcid: 4196065
doi: 10.5665/sleep.4178
Carroll, J. E. et al. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun 51, 223–229 (2016).
pubmed: 26336034
doi: 10.1016/j.bbi.2015.08.024
pmcid: 26336034
Gaspar, L. S., Álvaro, A. R., Moita, J. & Cavadas, C. Obstructive Sleep Apnea and Hallmarks of Aging. Trends in Molecular Medicine 23, 675–692 (2017).
pubmed: 28739207
doi: 10.1016/j.molmed.2017.06.006
pmcid: 28739207
Rohilla, A., Rohilla, S., Kumar, A., Khan, M. U. & Deep, A. Pleiotropic effects of statins: A boulevard to cardioprotection. Arabian Journal of Chemistry 9, S21–S27 (2016).
doi: 10.1016/j.arabjc.2011.06.025
Ramalingam, L. et al. The renin angiotensin system, oxidative stress and mitochondrial function in obesity and insulin resistance. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1863, 1106–1114 (2017).
doi: 10.1016/j.bbadis.2016.07.019
von Zglinicki, T., Saretzki, G., Ladhoff, J., d’Adda di Fagagna, F. & Jackson, S. P. Human cell senescence as a DNA damage response. Mech. Ageing Dev. 126, 111–117 (2005).
doi: 10.1016/j.mad.2004.09.034
d’Adda di Fagagna, F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 8, 512–522 (2008).
pubmed: 18574463
pmcid: 18574463
doi: 10.1038/nrc2440
Lavie, L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia – Revisited – The bad ugly and good: Implications to the heart and brain. Sleep Medicine Reviews 20, 27–45 (2015).
pubmed: 25155182
doi: 10.1016/j.smrv.2014.07.003
pmcid: 25155182
Zhang, J. & Veasey, S. Making Sense of Oxidative Stress in Obstructive Sleep Apnea: Mediator or Distracter? Front Neurol 3 (2012).
Nacarelli, T., Azar, A. & Sell, C. Mitochondrial stress induces cellular senescence in an mTORC1-dependent manner. Free Radic. Biol. Med. 95, 133–154 (2016).
pubmed: 27016071
doi: 10.1016/j.freeradbiomed.2016.03.008
pmcid: 27016071
Wiley, C. D. et al. Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab. 23, 303–314 (2016).
pubmed: 26686024
doi: 10.1016/j.cmet.2015.11.011
pmcid: 26686024
Shan, H., Bai, X. & Chen, X. Angiotensin II induces endothelial cell senescence via the activation of mitogen-activated protein kinases. Cell Biochem. Funct. 26, 459–466 (2008).
pubmed: 18383564
doi: 10.1002/cbf.1467
pmcid: 18383564
Herbert, K. E. et al. Angiotensin II–Mediated Oxidative DNA Damage Accelerates Cellular Senescence in Cultured Human Vascular Smooth Muscle Cells via Telomere-Dependent and Independent Pathways. Circ Res 102, 201–208 (2008).
pubmed: 17991883
doi: 10.1161/CIRCRESAHA.107.158626
pmcid: 17991883
Imanishi, T., Kobayashi, K., Kuroi, A., Ikejima, H. & Akasaka, T. Pioglitazone Inhibits Angiotensin II–Induced Senescence of Endothelial Progenitor Cell. Hypertens Res 31, 757–765 (2008).
pubmed: 18633188
doi: 10.1291/hypres.31.757
pmcid: 18633188
Imanishi, T., Hano, T. & Nishio, I. Estrogen Reduces Angiotensin II-Induced Acceleration of Senescence in Endothelial Progenitor Cells. Hypertens Res 28, 263–271 (2005).
pubmed: 16097371
doi: 10.1291/hypres.28.263
pmcid: 16097371
Min, L.-J. et al. Angiotensin II type 1 receptor-associated protein prevents vascular smooth muscle cell senescence via inactivation of calcineurin/nuclear factor of activated T cells pathway. J. Mol. Cell. Cardiol. 47, 798–809 (2009).
pubmed: 19769983
doi: 10.1016/j.yjmcc.2009.09.006
Ichiki, T. et al. Resveratrol attenuates angiotensin II-induced senescence of vascular smooth muscle cells. Regul. Pept. 177, 35–39 (2012).
pubmed: 22561451
doi: 10.1016/j.regpep.2012.04.005
Assmus, B. et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ. Res. 92, 1049–1055 (2003).
pubmed: 12676819
doi: 10.1161/01.RES.0000070067.64040.7C
Zhang, J.-J. et al. Atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats through a mechanism involving down-regulation of miR-21-5p/203a-3p. Mechanisms of Ageing and Development 169, 10–18 (2018).
pubmed: 29248491
doi: 10.1016/j.mad.2017.12.001
Ota, H. et al. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler. Thromb. Vasc. Biol. 30, 2205–2211 (2010).
pubmed: 20705918
doi: 10.1161/ATVBAHA.110.210500
Bode-Böger, S. M., Martens-Lobenhoffer, J., Täger, M., Schröder, H. & Scalera, F. Aspirin reduces endothelial cell senescence. Biochem. Biophys. Res. Commun. 334, 1226–1232 (2005).
pubmed: 16039999
doi: 10.1016/j.bbrc.2005.07.014
Banday, A. A. & Lokhandwala, M. F. Oxidative stress causes renal angiotensin II type 1 receptor upregulation, Na+/H+ exchanger 3 overstimulation, and hypertension. Hypertension 57, 452–459 (2011).
pubmed: 21282559
doi: 10.1161/HYPERTENSIONAHA.110.162339
Sungkaworn, T., Lenbury, Y. & Chatsudthipong, V. Oxidative stress increases angiotensin receptor type I responsiveness by increasing receptor degree of aggregation using image correlation spectroscopy. Biochimica et Biophysica Acta (BBA) - Biomembranes 1808, 2496–2500 (2011).
doi: 10.1016/j.bbamem.2011.07.007
De Mello, W. C. & Specht, P. Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart. J Renin Angiotensin Aldosterone Syst 7, 201–205 (2006).
pubmed: 17318788
doi: 10.3317/jraas.2006.038
Leung, P. S. Mechanisms of protective effects induced by blockade of the renin-angiotensin system: novel role of the pancreatic islet angiotensin-generating system in Type 2. diabetes. Diabet. Med. 24, 110–116 (2007).
pubmed: 17257271
doi: 10.1111/j.1464-5491.2007.02072.x
pmcid: 17257271
Frigolet, M. E., Torres, N. & Tovar, A. R. The renin–angiotensin system in adipose tissue and its metabolic consequences during obesity. The Journal of Nutritional Biochemistry 24, 2003–2015 (2013).
pubmed: 24120291
doi: 10.1016/j.jnutbio.2013.07.002
pmcid: 24120291
Hao, G. et al. Effects of ACEI/ARB in hypertensive patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled studies. BMC Cardiovasc Disord 14, 148 (2014).
pubmed: 25344747
pmcid: 4221690
doi: 10.1186/1471-2261-14-148
Hansson, L. et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. The Lancet 353, 611–616 (1999).
doi: 10.1016/S0140-6736(98)05012-0
Lindholm, L. H. et al. Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J. Hypertens. 20, 1879–1886 (2002).
pubmed: 12195132
doi: 10.1097/00004872-200209000-00035
pmcid: 12195132
Yusuf, S. et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med. 342, 145–153 (2000).
pubmed: 10639539
doi: 10.1056/NEJM200001203420301
pmcid: 10639539
Jakhar, R. & Crasta, K. Exosomes as Emerging Pro-Tumorigenic Mediators of the Senescence-Associated Secretory Phenotype. Int J Mol Sci 20 (2019).
Hoffmann, M. S., Singh, P., Wolk, R., Narkiewicz, K. & Somers, V. K. Obstructive Sleep Apnea and Intermittent Hypoxia Increase Expression of Dual Specificity Phosphatase 1. Atherosclerosis 231 (2013).
Sharma, P. et al. Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells. Sci Rep 8, 14110 (2018).
pubmed: 30237409
pmcid: 6148090
doi: 10.1038/s41598-018-32490-3
Becari, C., Teixeira, F. R., Oliveira, E. B. & Salgado, M. C. O. Angiotensin-converting enzyme inhibition augments the expression of rat elastase-2, an angiotensin II-forming enzyme. Am. J. Physiol. Heart Circ. Physiol. 301, H565–570 (2011).
pubmed: 21602471
doi: 10.1152/ajpheart.00534.2010
pmcid: 21602471
Oh, Y.-B., Kim, J. H., Park, B. M., Park, B. H. & Kim, S. H. Captopril intake decreases body weight gain via angiotensin-(1–7). Peptides 37, 79–85 (2012).
pubmed: 22743141
doi: 10.1016/j.peptides.2012.06.005
pmcid: 22743141
Becari, C. et al. Role of elastase-2 as an angiotensin II-forming enzyme in rat carotid artery. J. Cardiovasc. Pharmacol. 46, 498–504 (2005).
pubmed: 16160604
doi: 10.1097/01.fjc.0000177982.68563.98
pmcid: 16160604
Janke, J., Engeli, S., Gorzelniak, K., Luft, F. C. & Sharma, A. M. Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes 51, 1699–1707 (2002).
pubmed: 12031955
doi: 10.2337/diabetes.51.6.1699
pmcid: 12031955
Björkhem-Bergman, L., Lindh, J. D. & Bergman, P. What is a relevant statin concentration in cell experiments claiming pleiotropic effects? Br J Clin Pharmacol 72, 164–165 (2011).
pubmed: 21223360
pmcid: 3141200
doi: 10.1111/j.1365-2125.2011.03907.x
Su, Y.-F. et al. Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway. European Journal of Pharmacology 738, 101–110 (2014).
pubmed: 24726874
doi: 10.1016/j.ejphar.2014.03.009
pmcid: 24726874
De Luna-Bertos, E., Ramos-Torrecillas, J., García-Martínez, O., Díaz-Rodríguez, L. & Ruiz, C. Effect of Aspirin on Cell Growth of Human MG-63 Osteosarcoma Line. The Scientific World Journal, https://doi.org/10.1100/2012/834246 (2012).
Sarzani, R. et al. Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth. Int J Obes (Lond) 32, 259–267 (2008).
doi: 10.1038/sj.ijo.0803724
Abranches, E., Bekman, E., Henrique, D., Cabral, J. M. S. & Albranches, E. Expansion and neural differentiation of embryonic stem cells in adherent and suspension cultures. Biotechnol. Lett. 25, 725–730 (2003).
pubmed: 12882174
doi: 10.1023/A:1023462832608
pmcid: 12882174
Itahana, K., Campisi, J. & Dimri, G. P. Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol. Biol. 371, 21–31 (2007).
pubmed: 17634571
doi: 10.1007/978-1-59745-361-5_3
pmcid: 17634571
Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat Meth 9, 671–675 (2012).
doi: 10.1038/nmeth.2089
Jensen, E. C. Quantitative Analysis of Histological Staining and Fluorescence Using Image. J. Anat. Rec. 296, 378–381 (2013).
doi: 10.1002/ar.22641