Metabolomic signature of amino acids in plasma of patients with non-segmental Vitiligo

Metabolomics - Tập 17 - Trang 1-11 - 2021
Rezvan Marzabani1, Hassan Rezadoost1, Peyman Choopanian2, Sima Kolahdooz3, Nikoo Mozafari4, Mehdi Mirzaie5, Mehrdad Karimi3, Anni I. Nieminen6, Mohieddin Jafari5
1Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran
2Department of Applied Mathematics, Faculty of Mathematical Sciences, Tarbiat Modares University, Tehran, Iran
3School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
4Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
6Metabolomics Unit, Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland

Tóm tắt

Vitiligo pathogenesis is complicated, and several possibilities were suggested. However, it is well-known that the metabolism of pigments plays a significant role in the pathogenicity of the disease. We explored the role of amino acids in vitiligo using targeted metabolomics. The amino acid profile was studied in plasma using liquid chromatography. First, 22 amino acids were derivatized and precisely determined. Next, the concentrations of the amino acids and the molar ratios were calculated in 31 patients and 34 healthy individuals. The differential concentrations of amino acids were analyzed and eight amino acids, i.e., cysteine, arginine, lysine, ornithine, proline, glutamic acid, histidine, and glycine were observed differentially. The ratios of cysteine, glutamic acid, and proline increased significantly in Vitiligo patients, whereas arginine, lysine, ornithine, glycine, and histidine decreased significantly compared to healthy individuals. Considering the percentage of skin area, we also showed that glutamic acid significantly has a higher amount in patients with less than 25% involvement compared to others. Finally, cysteine and lysine are considered promising candidates for diagnosing and developing the disorder with high accuracy (0.96). The findings are consistent with the previously illustrated mechanism of Vitiligo, such as production deficiency in melanin and an increase in immune activity and oxidative stress. Furthermore, new evidence was provided by using amino acids profile toward the pathogenicity of the disorder.

Tài liệu tham khảo

Abumrad, N., A. Barbul (2004). The use of arginine in clinical practice. Metabolic and therapeutic aspects of amino acids in clinical nutrition, 595–611 Agarwal, S., Mendiratta, V., Chander, R., Jain, A., & Yadav, P. (2015). Study of serum levels of Vitamin B12, folic acid, and homocysteine in vitiligo. Pigment International, 2, 76. Akoglu, G., Neselioglu, S., Karaismailoglu, E., Aktas, A., & Erel, O. (2018). Plasma thiol levels are associated with disease severity in nonsegmental vitiligo. Indian Journal of Dermatology, 63, 323. Amiel, J. M., & Mathew, S. J. (2007). Glutamate and anxiety disorders. Current Psychiatry Reports, 9, 278–283. https://doi.org/10.1007/s11920-007-0033-7 Armstrong, A. (2011). Advances in Malignant Melanoma: Clinical and Research Perspectives, BoD–Books on Demand. Bansal, V., & Ochoa, J. B. (2003). Arginine availability, arginase, and the immune response. Current Opinion in Clinical Nutrition & Metabolic Care, 6, 223–228. Bergink, V., van Megen, H. J. G. M., & Westenberg, H. G. M. (2004). Glutamate and anxiety. European Neuropsychopharmacology, 14, 175–183. https://doi.org/10.1016/S0924-977X(03)00100-7 Binder, M. D., Hirokawa, N., & Windhorst, U. (2009). Encyclopedia of neuroscience (Vol. 3166). Springer. Coloff, J. L., et al. (2016). Differential glutamate metabolism in proliferating and quiescent mammary epithelial cells. Cell Metabolism, 23, 867–880. Cortese, B. M., & Phan, K. L. (2005). The role of glutamate in anxiety and related disorders. CNS Spectrums, 10, 820–830. https://doi.org/10.1017/s1092852900010427 De Fabo, E. C., & Noonan, F. P. (1983). Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology. Journal of Experimental Medicine, 158, 84–98. De Fabo, E. C., Webber, L. J., Ulman, E. A., & Broemeling, L. D. (1997). Dietary L-histidine regulates murine skin levels of trans-urocanic acid, an immune-regulating photoreceptor, with an unanticipated modulation: Potential relevance to skin cancer. The Journal of Nutrition, 127, 2158–2164. Ding, X., Du, J., & Zhang, J. (2014). The Epidemiology and Treatment of Vitiligo: A Chinese Perspective. Pigmentary Disorders, 1(2376–0427), 1000148. Ezzedine, K., et al. (2012). Revised classification/nomenclature of vitiligo and related issues: The Vitiligo Global Issues Consensus Conference. Pigment Cell & Melanoma Research, 25, E1–E13. Fekkes, D. (2012). Automated analysis of primary amino acids in plasma by high-performance liquid chromatography Amino Acid Analysis.(pp183–200). Springer. Flynn, N., Meininger, C., Haynes, T., & Wu, G. (2002). The metabolic basis of arginine nutrition and pharmacotherapy. Biomedicine & Pharmacotherapy, 56, 427–438. Gianfaldoni, S., et al. (2018). Unconventional treatments for Vitiligo: Are they (Un) satisfactory? Open Access Macedonian Journal of Medical Sciences, 6, 170. Gibbs, N. K., Tye, J., & Norval, M. (2008). Recent advances in urocanic acid photochemistry, photobiology and photoimmunology. Photochemical & Photobiological Sciences, 7, 655–667. Grimes, P., & Miller, M. (2018). Vitiligo: Patient stories, self-esteem, and the psychological burden of disease. International Journal of Women’s Dermatology, 4, 32–37. Hafez, M., & Sharaf, L. (1983). The genetics of vitiligo. Acta Dermato-Venereologica, 63, 249–251. Hamidizadeh, N., Ranjbar, S., Ghanizadeh, A., Parvizi, M. M., Jafari, P., & Handjani, F. (2020). Evaluating prevalence of depression, anxiety and hopelessness in patients with Vitiligo on an Iranian population. Health and Quality of Life Outcomes, 18, 20. Hamza, A. M., Farid, C. I., El-sayed, E. T., & Kadeeb, H. A. (2015). Assessment of serum homocysteine level in patients with nonsegmental vitiligo. Egyptian Journal of Dermatology and Venerology, 35, 59. Haug, K., et al. (2020). MetaboLights: A resource evolving in response to the needs of its scientific community. Nucleic Acids Research, 48, D440-d444. https://doi.org/10.1093/nar/gkz1019 Henning, S. W., et al. (2020). The relationship between stress and vitiligo: Evaluating perceived stress and electronic medical record data. PLoS ONE, 15, e0227909. Ito, S., Wakamatsu, K., & Ozeki, H. (2000). Chemical analysis of melanins and its application to the study of the regulation of melanogenesis. Pigment Cell Research, 13, 103–109. Jakku, R., Thappatla, V., Kola, T., & Kadarla, R. K. (2019). VITILIGO-An Overview. Asian Journal of Pharmaceutical Research and Development, 7, 124–132. Klemetti, P., et al. (2000). Autoimmunity to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED). Clinical & Experimental Immunology: Endocrine Disease, 119, 419–425. Kussainova, A., et al. (2020). Vitiligo and anxiety: A systematic review and meta-analysis. PLoS ONE, 15, e0241445. https://doi.org/10.1371/journal.pone.0241445 Liang, L., Li, Y., Tian, X., Zhou, J., & Zhong, L. (2019). Comprehensive lipidomic, metabolomic and proteomic profiling reveals the role of immune system in vitiligo. Clinical and Experimental Dermatology, 44, e216–e223. Liu, W., et al. (2020). Urinary metabolomic investigations in vitiligo patients. Scientific Reports, 10, 1–11. Malhotra, A. G., Jha, M., Singh, S., & Pandey, K. M. (2018). Construction of a comprehensive protein–protein interaction map for vitiligo disease to identify key regulatory elements: A systemic approach. Interdisciplinary Sciences: Computational Life Sciences, 10, 500–514. Mori, M. (2007). Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. The Journal of Nutrition, 137, 1616S-1620S. Murakami, H., Shimbo, K., Inoue, Y., Takino, Y., & Kobayashi, H. (2012). Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice. Amino Acids, 42, 2481–2489. Newsholme, P., Procopio, J., Lima, M. M. R., Pithon-Curi, T. C., & Curi, R. (2003). Glutamine and glutamate—their central role in cell metabolism and function. Cell Biochemistry and Function, 21, 1–9. Pekala, J., et al. (2011). L-carnitine-metabolic functions and meaning in humans life. Current Drug Metabolism, 12, 667–678. Phang, J. M. (2019). Proline metabolism in cell regulation and cancer biology: Recent advances and hypotheses. Antioxidants & Redox Signaling, 30, 635–649. Rath, M., Müller, I., Kropf, P., Closs, E. I., & Munder, M. (2014). Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Frontiers in Immunology, 5, 532. Rodrigues, M., K. Ezzedine, I. Hamzavi, A. G. Pandya, J. E. Harris, V. W. Group. (2017). New discoveries in the pathogenesis and classification of vitiligo. Journal of the American Academy of Dermatology, 77, 1–13. Roy, S. (2007). Melanin, melanogenesis, and vitiligo Progress in the Chemistry of Organic Natural Products.(pp131–185). Springer. Sabry, H. H., Sabry, J. H., & Hashim, H. M. (2014). Serum levels of homocysteine, vitamin B12, and folic acid in vitiligo. Egyptian Journal of Dermatology and Venerology, 34, 65–69. Sahoo, A., et al. (2017). MicroRNA-211 regulates oxidative phosphorylation and energy metabolism in human vitiligo. Journal of Investigative Dermatology, 137, 1965–1974. Seneschal, J., K. Boniface, A. D’Arino, M. Picardo (2020). An update on Vitiligo pathogenesis. Pigment cell & melanoma research, Shaker, O., & El-Tahlawi, S. (2008). Is there a relationship between homocysteine and vitiligo? A pilot study. British Journal of Dermatology, 159, 720–724. Simińska, E., & Koba, M. (2016). Amino acid profiling as a method of discovering biomarkers for early diagnosis of cancer. Amino Acids, 48, 1339–1345. Singh, R. K., et al. (2016). The role of IL-17 in vitiligo: A review. Autoimmunity Reviews, 15, 397–404. Singh, S., Singh, U., & Pandey, S. S. (2011). Increased level of serum homocysteine in vitiligo. Journal of Clinical Laboratory Analysis, 25, 110–112. Speeckaert, R., Speeckaert, M., De Schepper, S., & van Geel, N. (2017). Biomarkers of disease activity in vitiligo: A systematic review. Autoimmunity Reviews, 16, 937–945. Spritz, R. A., & Andersen, G. H. (2017). Genetics of vitiligo. Dermatologic Clinics, 35, 245–255. Taïeb, A., Picardo, M., & o. V. members, . (2007). The definition and assessment of vitiligo: A consensus report of the Vitiligo European Task Force. Pigment Cell Research, 20, 27–35. Vernwal, D. (2017). A study of anxiety and depression in Vitiligo patients: New challenges to treat. European Psychiatry, 41, S321–S321. Wu, G., et al. (2011). Proline and hydroxyproline metabolism: Implications for animal and human nutrition. Amino Acids, 40, 1053–1063. Wu, G., Bazer, F. W., Hu, J., Johnson, G. A., & Spencer, T. E. (2005). Polyamine synthesis from proline in the developing porcine placenta. Biology of Reproduction, 72, 842–850. Wu, J.-L., Yu, S.-Y., Wu, S.-H., & Bao, A.-M. (2016). A sensitive and practical RP-HPLC-FLD for determination of the low neuroactive amino acid levels in body fluids and its application in depression. Neuroscience Letters, 616, 32–37. Zheleva, A., Nikolova, G., Karamalakova, Y., Hristakieva, E., Lavcheva, R., & Gadjeva, V. (2018). Comparative study on some oxidative stress parameters in blood of vitiligo patients before and after combined therapy. Regulatory Toxicology and Pharmacology, 94, 234–239.