The erythrocyte membrane stability is associated with sleep time and social jetlag in shift workers

Autoři: Kely Raspante Cerqueira Teixeira aff001;  Luciana Alves de Medeiros aff002;  Jordane Amaral Mendes aff001;  Emília Rezende Vaz aff002;  Thúlio Marquez Cunha aff001;  Erick P. de Oliveira aff001;  Nilson Penha-Silva aff002;  Cibele Aparecida Crispim aff001
Působiště autorů: Faculty of Medicine, Federal University of Uberlândia, Uberlândia, MG, Brazil aff001;  Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222698


The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile.

Klíčová slova:

Blood – Circadian rhythms – Hemoglobin – Cholesterol – Red blood cells – Sleep – Erythrocyte membrane – Cytolysis


1. Gamble KL, Young ME. Metabolism as an integral cog in the mammalian circadian clockwork. Crit Rev Biochem Mol Biol. 2013;48(4):317–31. doi: 10.3109/10409238.2013.786672 23594144; PubMed Central PMCID: PMC3862897.

2. Schulz P, Steimer T. Neurobiology of circadian systems. CNS drugs. 2009;23 Suppl 2:3–13. doi: 10.2165/11318620-000000000-00000 19708721.

3. de Goede P, Wefers J, Brombacher EC, Schrauwen P, Kalsbeek A. Circadian rhythms in mitochondrial respiration. Journal of molecular endocrinology. 2018;60(3):R115–R30. doi: 10.1530/JME-17-0196 29378772; PubMed Central PMCID: PMC5854864.

4. Lu LF, Wang CP, Tsai IT, Hung WC, Yu TH, Wu CC, et al. Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers. J Occup Health. 2016;58(1):81–8. doi: 10.1539/joh.15-0137-OA 26549833.

5. Tai SY, Lin PC, Chen YM, Hung HC, Pan CH, Pan SM, et al. Effects of marital status and shift work on family function among registered nurses. Ind Health. 2014;52(4):296–303. doi: 10.2486/indhealth.2014-0009 24909112; PubMed Central PMCID: PMC4243015.

6. Waterhouse J, Buckley P, Edwards B, Reilly T. Measurement of, and some reasons for, differences in eating habits between night and day workers. Chronobiol Int. 2003;20(6):1075–92. 14680144.

7. Padilha HG, Crispim CA, Zimberg IZ, Folkard S, Tufik S, de Mello MT. Metabolic responses on the early shift. Chronobiol Int. 2010;27(5):1080–92. doi: 10.3109/07420528.2010.489883 20636217.

8. Schlafer O, Wenzel V, Hogl B. [Sleep disorders among physicians on shift work]. Der Anaesthesist. 2014;63(11):844–51. doi: 10.1007/s00101-014-2374-z 25213642.

9. Pietroiusti A, Neri A, Somma G, Coppeta L, Iavicoli I, Bergamaschi A, et al. Incidence of metabolic syndrome among night-shift healthcare workers. Occup Environ Med. 2010;67(1):54–7. doi: 10.1136/oem.2009.046797 19737731.

10. Foster RG, Wulff K. The rhythm of rest and excess. Nat Rev Neurosci. 2005;6(5):407–14. doi: 10.1038/nrn1670 15861183.

11. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22(6):1506–12. doi: 10.1093/humrep/dem046 17376819.

12. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106(11):4453–8. doi: 10.1073/pnas.0808180106 19255424; PubMed Central PMCID: PMC2657421.

13. Papantoniou K, Castano-Vinyals G, Espinosa A, Aragones N, Perez-Gomez B, Ardanaz E, et al. Breast cancer risk and night shift work in a case-control study in a Spanish population. Eur J Epidemiol. 2016;31(9):867–78. doi: 10.1007/s10654-015-0073-y 26205167.

14. Wittmann M, Dinich J, Merrow M, Roenneberg T. Social jetlag: misalignment of biological and social time. Chronobiol Int. 2006;23(1–2):497–509. doi: 10.1080/07420520500545979 16687322.

15. Roenneberg T, Merrow M. Entrainment of the human circadian clock. Cold Spring Harb Symp Quant Biol. 2007;72:293–9. doi: 10.1101/sqb.2007.72.043 18419286.

16. Roenneberg T, Allebrandt KV, Merrow M, Vetter C. Social jetlag and obesity. Curr Biol. 2012;22(10):939–43. doi: 10.1016/j.cub.2012.03.038 22578422.

17. Parsons MJ, Moffitt TE, Gregory AM, Goldman-Mellor S, Nolan PM, Poulton R, et al. Social jetlag, obesity and metabolic disorder: investigation in a cohort study. Int J Obes (Lond). 2015;39(5):842–8. doi: 10.1038/ijo.2014.201 25601363; PubMed Central PMCID: PMC4422765.

18. Rodrigues R, Alves de Medeiros L, Moreira Cunha L, da Silva Garrote-Filho M, Bernardino Neto M, Tannus Jorge P, et al. Correlations of the glycemic variability with oxidative stress and erythrocytes membrane stability in patients with type 1 diabetes under intensive treatment. Diabetes Res Clin Pract. 2018. doi: 10.1016/j.diabres.2018.01.031 29427698.

19. Osuntokl AA, Fasanmade OA, Adekola AO, Amira CO. Lipid peroxidation and erythrocyte fragility in poorly controlled type 2 diabetes mellitus. Nig Q J Hosp Med. 2007;17(4):148–51. 18320761.

20. da Silva Garrote-Filho M, Bernardino-Neto M, Penha-Silva N. Influence of Erythrocyte Membrane Stability in Atherosclerosis. Curr Atheroscler Rep. 2017;19(4):17. doi: 10.1007/s11883-017-0653-2 28243806.

21. Gaikwad SS, Avari JG. Effect On Morphology, Osmotic Fragility And Electro Kinetic Potential Of Erythrocytes In Hypertension. Curr Hypertens Rev. 2017. doi: 10.2174/1573402113666170911140747 28901247.

22. Wide L, Bengtsson C, Birgegard G. Circadian rhythm of erythropoietin in human serum. Br J Haematol. 1989;72(1):85–90. doi: 10.1111/j.1365-2141.1989.tb07657.x 2736245.

23. O'Neill JS, Reddy AB. Circadian clocks in human red blood cells. Nature. 2011;469(7331):498–503. doi: 10.1038/nature09702 21270888; PubMed Central PMCID: PMC3040566.

24. Henslee EA, Crosby P, Kitcatt SJ, Parry JSW, Bernardini A, Abdallat RG, et al. Rhythmic potassium transport regulates the circadian clock in human red blood cells. Nature communications. 2017;8(1):1978. doi: 10.1038/s41467-017-02161-4 29215003; PubMed Central PMCID: PMC5719349.

25. Mohandas N, Gallagher PG. Red cell membrane: past, present, and future. Blood. 2008;112(10):3939–48. doi: 10.1182/blood-2008-07-161166 18988878; PubMed Central PMCID: PMC2582001.

26. Bernardino Neto M, de Avelar EB Jr., Arantes TS, Jordao IA, da Costa Huss JC, de Souza TM, et al. Bivariate and multivariate analyses of the correlations between stability of the erythrocyte membrane, serum lipids and hematological variables. Biorheology. 2013;50(5–6):305–20. doi: 10.3233/BIR-130641 24398611.

27. Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behavior research methods. 2009;41(4):1149–60. doi: 10.3758/BRM.41.4.1149 19897823.

28. WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1–253. 11234459.

29. WHO. Waist circumference and waist–hip ratio: report of a WHO expert consultation. In: World Health Organization W, editor. Geneva2008.

30. Mota MC, Silva CM, Balieiro LCT, Fahmy WM, Crispim CA. Social jetlag and metabolic control in non-communicable chronic diseases: a study addressing different obesity statuses. Sci Rep. 2017;7(1):6358. doi: 10.1038/s41598-017-06723-w 28743872; PubMed Central PMCID: PMC5526860.

31. Reutrakul S, Hood MM, Crowley SJ, Morgan MK, Teodori M, Knutson KL, et al. Chronotype is independently associated with glycemic control in type 2 diabetes. Diabetes Care. 2013;36(9):2523–9. doi: 10.2337/dc12-2697 23637357; PubMed Central PMCID: PMC3747872.

32. Juda M, Vetter C, Roenneberg T. The Munich ChronoType Questionnaire for Shift-Workers (MCTQShift). J Biol Rhythms. 2013;28(2):130–40. doi: 10.1177/0748730412475041 23606612.

33. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540–5. doi: 10.1093/sleep/14.6.540 1798888.

34. Bertolazi AN. Tradução, adaptação cultural e validação de dois instrumentos de avaliação Do sono: Escala de Sonolência de Epworth e Índice de Qualidade de sono de Pittsburgh. Porto Alegre: Universidade Federal do Rio Grande do Sul.; 2008.

35. Kendzerska TB, Smith PM, Brignardello-Petersen R, Leung RS, Tomlinson GA. Evaluation of the measurement properties of the Epworth sleepiness scale: a systematic review. Sleep Med Rev. 2014;18(4):321–31. doi: 10.1016/j.smrv.2013.08.002 24135493.

36. de Freitas MV, Netto Rde C, da Costa Huss JC, de Souza TM, Costa JO, Firmino CB, et al. Influence of aqueous crude extracts of medicinal plants on the osmotic stability of human erythrocytes. Toxicology in vitro: an international journal published in association with BIBRA. 2008;22(1):219–24. doi: 10.1016/j.tiv.2007.07.010 17855047.

37. Mascarenhas Netto Rde C, Fabbri C, de Freitas MV, Bernardino Neto M, Garrote-Filho MS, Lacerda MV, et al. Influence of Plasmodium vivax malaria on the relations between the osmotic stability of human erythrocyte membrane and hematological and biochemical variables. Parasitology research. 2014;113(3):863–74. doi: 10.1007/s00436-013-3717-4 24322291.

38. Penha-Silva N, Firmino CB, de Freitas Reis FG, da Costa Huss JC, de Souza TM, de Freitas MV, et al. Influence of age on the stability of human erythrocyte membranes. Mechanisms of ageing and development. 2007;128(7–8):444–9. doi: 10.1016/j.mad.2007.06.007 17681589.

39. Paraiso LF, Goncalves EOAF, Cunha LM, de Almeida Neto OP, Pacheco AG, Araujo KB, et al. Effects of acute and chronic exercise on the osmotic stability of erythrocyte membrane of competitive swimmers. PloS one. 2017;12(2):e0171318. doi: 10.1371/journal.pone.0171318 28151958; PubMed Central PMCID: PMC5289559.

40. Benjamini Y, Hochberg Y. Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc Ser B-Methodological. 1995;57:289–300. doi: 10.2307/2346101

41. Aires Rodrigues de Freitas M, Vieira da Costa A, Alves de Medeiros L, da Silva Garrote Filho M, Lemos Debs Diniz A, Penha-Silva N. Are There Differences in the Anthropometric, Hemodynamic, Hematologic, and Biochemical Profiles between Late- and Early-Onset Preeclampsia? Obstetrics and gynecology international. 2018;2018:9628726. doi: 10.1155/2018/9628726 29686709; PubMed Central PMCID: PMC5852893.

42. Cooper RA. Influence of increased membrane cholesterol on membrane fluidity and cell function in human red blood cells. J Supramol Struct. 1978;8(4):413–30. doi: 10.1002/jss.400080404 723275.

43. Koter M, Franiak I, Strychalska K, Broncel M, Chojnowska-Jezierska J. Damage to the structure of erythrocyte plasma membranes in patients with type-2 hypercholesterolemia. Int J Biochem Cell Biol. 2004;36(2):205–15. 14643886.

44. Marks PA, Johnson AB. Relationship between the age of human erythrocytes and their osmotic resistance: a basis for separating young and old erythrocytes. J Clin Invest. 1958;37(11):1542–8. doi: 10.1172/JCI103746 13587663; PubMed Central PMCID: PMC1062836.

45. de Freitas MV, de Oliveira MR, dos Santos DF, de Cassia Mascarenhas Netto R, Fenelon SB, Penha-Silva N. Influence of the use of statin on the stability of erythrocyte membranes in multiple sclerosis. J Membr Biol. 2010;233(1–3):127–34. doi: 10.1007/s00232-010-9232-y 20146058.

46. Hui SW, Stewart CM, Carpenter MP, Stewart TP. Effects of cholesterol on lipid organization in human erythrocyte membrane. J Cell Biol. 1980;85(2):283–91. doi: 10.1083/jcb.85.2.283 7372709; PubMed Central PMCID: PMC2110611.

47. Chua EC, Shui G, Cazenave-Gassiot A, Wenk MR, Gooley JJ. Changes in Plasma Lipids during Exposure to Total Sleep Deprivation. Sleep. 2015;38(11):1683–91. doi: 10.5665/sleep.5142 26194579; PubMed Central PMCID: PMC4813350.

48. Lemke MK, Apostolopoulos Y, Hege A, Wideman L, Sonmez S. Work, sleep, and cholesterol levels of U.S. long-haul truck drivers. Ind Health. 2017;55(2):149–61. doi: 10.2486/indhealth.2016-0127 28049935; PubMed Central PMCID: PMC5383412.

49. Loprinzi PD. Sleep duration and sleep disorder with red blood cell distribution width. Am J Health Behav. 2015;39(4):471–4. doi: 10.5993/AJHB.39.4.3 26018095.

50. Lippi G, Plebani M. Red blood cell distribution width (RDW) and human pathology. One size fits all. Clin Chem Lab Med. 2014;52(9):1247–9. doi: 10.1515/cclm-2014-0585 24945432.

51. Park KI, Kim KY. Clinical evaluation of red cell volume distribution width (RDW). Yonsei Med J. 1987;28(4):282–90. doi: 10.3349/ymj.1987.28.4.282 3439197.

52. Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: A simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci. 2015;52(2):86–105. doi: 10.3109/10408363.2014.992064 25535770.

53. Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseases. J Thorac Dis. 2015;7(10):E402–11. doi: 10.3978/j.issn.2072-1439.2015.10.04 26623117; PubMed Central PMCID: PMC4635283.

54. Li N, Zhou H, Tang Q. Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases. Dis Markers. 2017;2017:7089493. doi: 10.1155/2017/7089493 29038615; PubMed Central PMCID: PMC5606102.

55. Su C, Liao LZ, Song Y, Xu ZW, Mei WY. The role of red blood cell distribution width in mortality and cardiovascular risk among patients with coronary artery diseases: a systematic review and meta-analysis. J Thorac Dis. 2014;6(10):1429–40. doi: 10.3978/j.issn.2072-1439.2014.09.10 25364520; PubMed Central PMCID: PMC4215144.

56. Bujak K, Wasilewski J, Osadnik T, Jonczyk S, Kolodziejska A, Gierlotka M, et al. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology. Dis Markers. 2015;2015:824624. doi: 10.1155/2015/824624 26379362; PubMed Central PMCID: PMC4563066.

57. Wonnerth A, Krychtiuk KA, Mayer FJ, Minar E, Wojta J, Schillinger M, et al. Red cell distribution width and mortality in carotid atherosclerosis. Eur J Clin Invest. 2016;46(2):198–204. doi: 10.1111/eci.12584 26709235.

58. Tziakas D, Chalikias G, Grapsa A, Gioka T, Tentes I, Konstantinides S. Red blood cell distribution width: a strong prognostic marker in cardiovascular disease: is associated with cholesterol content of erythrocyte membrane. Clin Hemorheol Microcirc. 2012;51(4):243–54. doi: 10.3233/CH-2012-1530 22277951.

59. Tziakas DN, Chalikias GK, Stakos D, Boudoulas H. The role of red blood cells in the progression and instability of atherosclerotic plaque. Int J Cardiol. 2010;142(1):2–7. doi: 10.1016/j.ijcard.2009.10.031 19906450.

60. Burgueno A, Gemma C, Gianotti TF, Sookoian S, Pirola CJ. Increased levels of resistin in rotating shift workers: a potential mediator of cardiovascular risk associated with circadian misalignment. Atherosclerosis. 2010;210(2):625–9. doi: 10.1016/j.atherosclerosis.2009.12.032 20106477.

61. Puttonen S, Viitasalo K, Harma M. Effect of shiftwork on systemic markers of inflammation. Chronobiol Int. 2011;28(6):528–35. doi: 10.3109/07420528.2011.580869 21797781.

62. Lasselin J, Rehman JU, Akerstedt T, Lekander M, Axelsson J. Effect of long-term sleep restriction and subsequent recovery sleep on the diurnal rhythms of white blood cell subpopulations. Brain Behav Immun. 2015;47:93–9. doi: 10.1016/j.bbi.2014.10.004 25451611.

63. Pritchett D, Reddy AB. Circadian Clocks in the Hematologic System. J Biol Rhythms. 2015;30(5):374–88. doi: 10.1177/0748730415592729 26163380.

64. Dinarelli S, Longo G, Dietler G, Francioso A, Mosca L, Pannitteri G, et al. Erythrocyte's aging in microgravity highlights how environmental stimuli shape metabolism and morphology. Sci Rep. 2018;8(1):5277. doi: 10.1038/s41598-018-22870-0 29588453; PubMed Central PMCID: PMC5869709.

65. Oishi K, Ohkura N, Kadota K, Kasamatsu M, Shibusawa K, Matsuda J, et al. Clock mutation affects circadian regulation of circulating blood cells. J Circadian Rhythms. 2006;4:13. doi: 10.1186/1740-3391-4-13 17014730; PubMed Central PMCID: PMC1592512.

66. Haus E, Lakatua DJ, Swoyer J, Sackett-Lundeen L. Chronobiology in hematology and immunology. Am J Anat. 1983;168(4):467–517. doi: 10.1002/aja.1001680406 6364772.

67. Kantermann T, Wehrens SM, Ulhoa MA, Moreno C, Skene DJ. Noisy and individual, but doable: shift-work research in humans. Prog Brain Res. 2012;199:399–411. doi: 10.1016/B978-0-444-59427-3.00022-8 22877677.

68. Vetter C, Fischer D, Matera JL, Roenneberg T. Aligning work and circadian time in shift workers improves sleep and reduces circadian disruption. Curr Biol. 2015;25(7):907–11. doi: 10.1016/j.cub.2015.01.064 25772446.

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