Skip to main content

Advertisement

Log in

A Pilot Urinary Proteome Study Reveals Widespread Influences of Circadian Rhythm Disruption by Sleep Deprivation

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

It is widely accepted that circadian rhythm disruption caused short- or long-term adverse effects on health. Although many previous studies have focused on exploration of the molecular mechanisms, there is no rapid, convenient, and non-invasive method to reveal the influence on health after circadian rhythm disruption. Here, we performed a high-resolution mass spectrometry-based data-independent acquisition (DIA) quantitative urinary proteomic approach in order to explore whether urine could reveal stress changes to those brought about by circadian rhythm disruption after sleep deprivation. After sleep deprivation, the subjects showed a significant increase in both systolic and diastolic blood pressure compared with routine sleep. More than 2000 proteins were quantified and they contained specific proteins for various organs throughout the body. And a total of 177 significantly up-regulated proteins and 68 significantly down-regulated proteins were obtained after sleep deprivation. These differentially expressed proteins (DEPs) were associated with multiple organs and pathways, which reflected widespread influences of sleep deprivation. Besides, machine learning identified a panel of five DEPs (CD300A, SCAMP3, TXN2, EFEMP1, and MYH11) that can effectively discriminate circadian rhythm disruption. Taken together, our results validate the value of urinary proteome in predicting and diagnosing the changes by circadian rhythm disruption.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the iProX [69] partner repository with the dataset identifier PXD038035.

References

  1. Bass, J., & Takahashi, J. S. (2010). Circadian integration of metabolism and energetics. Science, 330(6009), 1349–1354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Allada, R., & Bass, J. (2021). Circadian mechanisms in medicine. New England Journal of Medicine, 384(6), 550–561.

    Article  CAS  PubMed  Google Scholar 

  3. Bass, J., & Lazar, M. A. (2016). Circadian time signatures of fitness and disease. Science, 354(6315), 994–999.

    Article  CAS  PubMed  Google Scholar 

  4. Morris, C. J., et al. (2016). Circadian misalignment increases cardiovascular disease risk factors in humans. Proceedings of the National Academy of Sciences U S A, 113(10), E1402–E1411.

    Article  CAS  Google Scholar 

  5. Zhao, Y., et al. (2022). Disruption of circadian rhythms by shift work exacerbates reperfusion injury in myocardial infarction. Journal of the American College of Cardiology, 79(21), 2097–2115.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chellappa, S. L., et al. (2019). Impact of circadian disruption on cardiovascular function and disease. Trends in Endocrinology and Metabolism, 30(10), 767–779.

    Article  CAS  PubMed  Google Scholar 

  7. Thosar, S. S., Butler, M. P., & Shea, S. A. (2018). Role of the circadian system in cardiovascular disease. The Journal of Clinical Investigation, 128(6), 2157–2167.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Leng, Y., et al. (2019). Association between circadian rhythms and neurodegenerative diseases. Lancet Neurology, 18(3), 307–318.

    Article  PubMed  Google Scholar 

  9. Wu, H., et al. (2019). The role of sleep deprivation and circadian rhythm disruption as risk factors of Alzheimer’s disease. Frontiers in Neuroendocrinology, 54, 100764.

    Article  PubMed  Google Scholar 

  10. Kettner, N. M., et al. (2016). Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell, 30(6), 909–924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pan, A., et al. (2011). Rotating night shift work and risk of type 2 diabetes: Two prospective cohort studies in women. PLoS Medicine, 8(12), e1001141.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hansen, J. (2017). Night shift work and risk of breast cancer. Current Environmental Health Reports, 4(3), 325–339.

    Article  PubMed  Google Scholar 

  13. Medic, G., Wille, M., & Hemels, M. (2017). Short- and long-term health consequences of sleep disruption. 9, 151–161.

  14. Hastings, M. H. (1997). Central clocking. Trends in Neurosciences, 20(10), 459–464.

    Article  CAS  PubMed  Google Scholar 

  15. Inouye, S. I. T., & Kawamura, H. (1982). Characteristics of a circadian pacemaker in the suprachiasmatic nucleus. Journal of Comparative Physiology, 146(2), 153–160.

    Article  Google Scholar 

  16. Ralph, M. R., et al. (1990). Transplanted suprachiasmatic nucleus determines circadian period. Science, 247(4945), 975–978.

    Article  CAS  PubMed  Google Scholar 

  17. Ruan, W., Yuan, X., & Eltzschig, H. K. (2021). Circadian rhythm as a therapeutic target. Nature Reviews Drug Discovery, 20(4), 287–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hardin, P. E., Hall, J. C., & Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature, 343(6258), 536–540.

    Article  CAS  PubMed  Google Scholar 

  19. Partch, C. L., Green, C. B., & Takahashi, J. S. (2014). Molecular architecture of the mammalian circadian clock. Trends in Cell Biology, 24(2), 90–99.

    Article  CAS  PubMed  Google Scholar 

  20. Hughes, S., et al. (2015). Photic regulation of clock systems. Methods in Enzymology, 552, 125–143.

    Article  CAS  PubMed  Google Scholar 

  21. Gekakis, N., et al. (1998). Role of the CLOCK protein in the mammalian circadian mechanism. Science, 280(5369), 1564–1569.

    Article  CAS  PubMed  Google Scholar 

  22. Richardson, G. S. (2005). The human circadian system in normal and disordered sleep. The Journal of Clinical Psychiatry, 66(Suppl 9), 3.

    PubMed  Google Scholar 

  23. Hudson, A. N., Van Dongen, H. P. A., & Honn, K. A. (2020). Sleep deprivation, vigilant attention, and brain function: a review. Neuropsychopharmacology (New York, N.Y.), 45(1), 21–30.

    Google Scholar 

  24. Nakata, A. (2011). Effects of long work hours and poor sleep characteristics on workplace injury among full-time male employees of small- and medium-scale businesses. Journal of Sleep Research, 20(4), 576–584.

    Article  PubMed  Google Scholar 

  25. Bhadra, U., et al. (2017). Evolution of circadian rhythms: From bacteria to human. Sleep Medicine, 35, 49–61.

    Article  PubMed  Google Scholar 

  26. Matenchuk, B. A., Mandhane, P. J., & Kozyrskyj, A. L. (2020). Sleep, circadian rhythm, and gut microbiota. Sleep Medicine Reviews, 53, 101340.

    Article  PubMed  Google Scholar 

  27. Liu, H., & Chen, A. (2019). Roles of sleep deprivation in cardiovascular dysfunctions. Life Sciences, 219, 231–237.

    Article  CAS  PubMed  Google Scholar 

  28. Moreno-Villanueva, M., et al. (2018). The degree of radiation-induced DNA strand breaks is altered by acute sleep deprivation and psychological stress and is associated with cognitive performance in humans. Sleep, 41(7).

  29. Bader, J. M., et al. (2020). Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer’s disease. Molecular Systems Biology, 16(6), e9356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wu, J., et al. (2021). Proteomics applications in biomarker discovery and pathogenesis for abdominal aortic aneurysm. Expert Review of Proteomics, 18(4), 305–314.

    Article  CAS  PubMed  Google Scholar 

  31. Risha, Y., et al. (2020). The proteomic analysis of breast cell line exosomes reveals disease patterns and potential biomarkers. Science and Reports, 10(1), 13572.

    Article  CAS  Google Scholar 

  32. Zhao, M., et al. (2017). A comprehensive analysis and annotation of human normal urinary proteome. Science and Reports, 7(1), 3024.

    Article  Google Scholar 

  33. Gao, Y. (2013). Urine-an untapped goldmine for biomarker discovery? Science China Life Sciences, 56(12), 1145–1146.

    Article  PubMed  Google Scholar 

  34. Virreira, W. S., et al. (2021). Urinary proteome profiling for stratifying patients with familial Parkinson’s disease. EMBO Molecular Medicine, 13(3), e13257.

    Article  Google Scholar 

  35. Ferrari, E., et al. (2019). Urinary proteomics profiles are useful for detection of cancer biomarkers and changes induced by therapeutic procedures. Molecules, 24(4), 794.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Duangkumpha, K., et al. (2019). Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis. PLoS One, 14(8), e0221024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Depner, C. M., et al. (2018). Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome. Proceedings of the National Academy of Sciences, 115(23).

  38. Liu, T., et al. (2022). B serum proteome profiles revealed dysregulated proteins and mechanisms associated with insomnia patients: a preliminary study. Frontiers in Integrative Neuroscience, 16.

  39. Geyer, P. E., et al. (2019). Plasma proteome profiling to detect and avoid sample-related biases in biomarker studies. EMBO Molecular Medicine, 11(11), e10427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Adachi, J., et al. (2006). The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins. Genome Biology, 7(9), R80.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Geyer, P. E., et al. (2016). Plasma proteome profiling to assess human health and disease. Cell Systems, 2(3), 185–195.

    Article  CAS  PubMed  Google Scholar 

  42. Wang, D., et al. (2019). A deep proteome and transcriptome abundance atlas of 29 healthy human tissues. Molecular Systems Biology, 15(2), e8503.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Uhlen, M., et al. (2015). Proteomics. Tissue-based map of the human proteome. Science, 347(6220), 1260419.

    Article  PubMed  Google Scholar 

  44. Cao, R., et al. (2015). Light-regulated translational control of circadian behavior by eIF4E phosphorylation. Nature Neuroscience, 18(6), 855–862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. D’Abronzo, L. S., & Ghosh, P. M. (2018). eIF4E phosphorylation in prostate cancer. Neoplasia, 20(6), 563–573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Knight, J. R. P., et al. (2021). MNK inhibition sensitizes KRAS-mutant colorectal cancer to mTORC1 inhibition by reducing eIF4E phosphorylation and c-MYC expression. Cancer Discovery, 11(5), 1228–1247.

    Article  CAS  PubMed  Google Scholar 

  47. Gong, C., et al. (2020). Phosphorylation independent eIF4E translational reprogramming of selective mRNAs determines tamoxifen resistance in breast cancer. Oncogene, 39(15), 3206–3217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Piserà, A., Campo, A., & Campo, S. (2018). Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment. Journal of Genetics and Genomics, 45(1), 13–24.

    Article  PubMed  Google Scholar 

  49. Guo, Q., et al. (2021). The MNK1/2–eIF4E axis supports immune suppression and metastasis in postpartum breast cancer. Cancer Research, 81(14), 3876–3889.

    Article  CAS  PubMed  Google Scholar 

  50. Peek, C. B., et al. (2017). Circadian clock interaction with HIF1α mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle. Cell Metabolism, 25(1), 86–92.

    Article  CAS  PubMed  Google Scholar 

  51. Deng, W., et al. (2018). The circadian clock controls immune checkpoint pathway in sepsis. Cell Reports, 24(2), 366–378.

    Article  CAS  PubMed  Google Scholar 

  52. Yuan, P., et al. (2020). Circadian clock gene NPAS2 promotes reprogramming of glucose metabolism in hepatocellular carcinoma cells. Cancer Letters, 469, 498–509.

    Article  CAS  PubMed  Google Scholar 

  53. Yu, M., et al. (2018). Circadian regulator NR1D2 regulates glioblastoma cell proliferation and motility. Oncogene, 37(35), 4838–4853.

    Article  CAS  PubMed  Google Scholar 

  54. Jiang, L., et al. (2020). A quantitative proteome map of the human body. Cell, 183(1), 269-283.e19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Edfors, F., et al. (2016). Gene-specific correlation of RNA and protein levels in human cells and tissues. Molecular Systems Biology, 12(10), 883.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Qin, W., et al. (2022). Proteome analysis of urinary biomarkers in a cigarette smoke-induced COPD rat model. Respiratory Research, 23(1), 156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cao, Y., et al. (2021). CD300a and CD300f molecules regulate the function of leukocytes. International Immunopharmacology, 93, 107373.

    Article  CAS  PubMed  Google Scholar 

  58. Lu, J. Y., et al. (2021). Secretory carrier membrane protein 3 interacts with 3A viral protein of enterovirus and participates in viral replication. Microbiology Spectrum, 9(1), e0047521.

    Article  PubMed  Google Scholar 

  59. Li, H., et al. (2017). Thioredoxin 2 offers protection against mitochondrial oxidative stress in H9c2 cells and against myocardial hypertrophy induced by hyperglycemia. International Journal of Molecular Sciences, 18(9), 1958.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Holzerova, E., et al. (2016). Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration. Brain, 139(2), 346–354.

    Article  PubMed  Google Scholar 

  61. Han, A. L., et al. (2017). Fibulin-3 promotes muscle-invasive bladder cancer. Oncogene, 36(37), 5243–5251.

    Article  CAS  PubMed  Google Scholar 

  62. Kim, I. G., et al. (2014). Fibulin-3-mediated inhibition of epithelial-to-mesenchymal transition and self-renewal of ALDH+ lung cancer stem cells through IGF1R signaling. Oncogene, 33(30), 3908–3917.

    Article  CAS  PubMed  Google Scholar 

  63. Blue, E. E., et al. (2021). Non-coding variants inMYH11, FZD3, andSORCS3 are associated with dementia in women. Alzheimer’s & Dementia, 17(2), 215–225.

    Article  CAS  Google Scholar 

  64. Barwinska, D., et al. (2021). Molecular characterization of the human kidney interstitium in health and disease. Science Advances, 7(7).

  65. Shen, B., et al. (2020). Proteomic and metabolomic characterization of COVID-19 patient sera. Cell, 182(1), 59-72 e15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Shao, C., et al. (2019). Comprehensive analysis of individual variation in the urinary proteome revealed significant gender differences. Molecular and Cellular Proteomics, 18(6), 1110–1122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bailey, M., & Silver, R. (2014). Sex differences in circadian timing systems: Implications for disease. Frontiers in Neuroendocrinology, 35(1), 111–139.

    Article  PubMed  Google Scholar 

  68. Tian, W., et al. (2020). Immune suppression in the early stage of COVID-19 disease. Nature Communications, 11(1).

  69. Ma, J., et al. (2019). iProX: An integrated proteome resource. Nucleic Acids Research, 47(D1), D1211–D1217.

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation (32171431).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: LX. Methodology: XL, LM, and QF. Formal analysis: LZ, LX, and SM. Investigation: XL, ZH, YW, and LZ. Data curation: LZ, XW, LX, and SM. Writing—original draft preparation: LZ and SM. Writing—review and editing: LX, XW, and SM. Funding acquisition: LX and XL.

Corresponding authors

Correspondence to Li Xia or Shuang Meng.

Ethics declarations

Ethics Approval

This study had been approved by the ethics committee of Shanghai Jiao Tong University School of Medicine with No. 2022-A-05.

Consent to Participate

All participants volunteered to participate in this study, and informed consent had been obtained from them.

Consent for Publication

All authors agree to publish their work.

Conflicts of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 868 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, L., Lu, X., Wang, X. et al. A Pilot Urinary Proteome Study Reveals Widespread Influences of Circadian Rhythm Disruption by Sleep Deprivation. Appl Biochem Biotechnol 196, 1992–2011 (2024). https://doi.org/10.1007/s12010-023-04666-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04666-9

Keywords

Navigation