Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Neuropeptidomics: Mass Spectrometry-Based Identification and Quantitation of Neuropeptides

  • Lee, Ji Eun (Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology)
  • Received : 2016.01.05
  • Accepted : 2016.03.03
  • Published : 2016.03.31
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Abstract

Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides.

Keywords

References

  1. Hokfelt T, Broberger C, Xu ZQ, Sergeyev V, Ubink R, Diez M. Neuropeptides: an overview. Neuropharmacology 2000;39:1337-1356. https://doi.org/10.1016/S0028-3908(00)00010-1
  2. Fricker LD. Neuropeptides and Other Bioactive Peptides: from Discovery to Function. San Rafael: Morgan & Claypool Life Sciences, 2012.
  3. Hokfelt T, Bartfai T, Bloom F. Neuropeptides: opportunities for drug discovery. Lancet Neurol 2003;2:463-472. https://doi.org/10.1016/S1474-4422(03)00482-4
  4. De Wied D. Long term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature 1971;232:58-60. https://doi.org/10.1038/232058a0
  5. Le TT, Lehnert S, Colgrave ML. Neuropeptidomics applied to studies of mammalian reproduction. Peptidomics 2013;1:1-13.
  6. Fricker LD, Lim J, Pan H, Che FY. Peptidomics: identification and quantification of endogenous peptides in neuroendocrine tissues. Mass Spectrom Rev 2006;25:327-344. https://doi.org/10.1002/mas.20079
  7. Prigge ST, Mains RE, Eipper BA, Amzel LM. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell Mol Life Sci 2000;57:1236-1259. https://doi.org/10.1007/PL00000763
  8. Huttner WB. Tyrosine sulfation and the secretory pathway. Annu Rev Physiol 1988;50:363-376. https://doi.org/10.1146/annurev.ph.50.030188.002051
  9. Veo K, Reinick C, Liang L, Moser E, Angleson JK, Dores RM. Observations on the ligand selectivity of the melanocortin 2 receptor. Gen Comp Endocrinol 2011;172:3-9. https://doi.org/10.1016/j.ygcen.2011.04.006
  10. Eipper BA, Mains RE. Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides. Endocr Rev 1980;1:1-27. https://doi.org/10.1210/edrv-1-1-1
  11. Eipper BA, Mains RE, Herbert E. Peptides in the nervous system. Trends Neurosci 1986;9:463-468. https://doi.org/10.1016/0166-2236(86)90149-9
  12. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660. https://doi.org/10.1038/45230
  13. Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 2003;24:580-588. https://doi.org/10.1016/j.tips.2003.09.011
  14. van den Pol AN. Neuropeptide transmission in brain circuits. Neuron 2012;76:98-115. https://doi.org/10.1016/j.neuron.2012.09.014
  15. Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005;4:141-194. https://doi.org/10.1016/j.arr.2005.03.003
  16. Clynen E, Swijsen A, Raijmakers M, Hoogland G, Rigo JM. Neuropeptides as targets for the development of anticonvulsant drugs. Mol Neurobiol 2014;50:626-646. https://doi.org/10.1007/s12035-014-8669-x
  17. Werner FM. Classical neurotransmitters and neuropeptides involved in Parkinson's disease. Parkinsonism Relat Disord 2007;13 Suppl 2:S97.
  18. Barson JR, Leibowitz SF. Hypothalamic neuropeptide signaling in alcohol addiction. Prog Neuropsychopharmacol Biol Psychiatry 2016;65:321-329. https://doi.org/10.1016/j.pnpbp.2015.02.006
  19. Peters EM, Ericson ME, Hosoi J, Seiffert K, Hordinsky MK, Ansel JC, et al. Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance. J Invest Dermatol 2006;126:1937-1947. https://doi.org/10.1038/sj.jid.5700429
  20. Tatemoto K. Neuropeptide Y: complete amino acid sequence of the brain peptide. Proc Natl Acad Sci U S A 1982;79:5485-5489. https://doi.org/10.1073/pnas.79.18.5485
  21. Lovejoy DA, Fischer WH, Ngamvongchon S, Craig AG, Nahorniak CS, Peter RE, et al. Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution. Proc Natl Acad Sci U S A 1992;89:6373-6377. https://doi.org/10.1073/pnas.89.14.6373
  22. Hummon AB, Amare A, Sweedler JV. Discovering new invertebrate neuropeptides using mass spectrometry. Mass Spectrom Rev 2006;25:77-98. https://doi.org/10.1002/mas.20055
  23. Stenfors C, Mathe AA, Theodorsson E. Chromatographic and immunochemical characterization of rat brain neuropeptide Y-like immunoreactivity (NPY-LI) following repeated electroconvulsive stimuli. J Neurosci Res 1995;41:206-212. https://doi.org/10.1002/jnr.490410208
  24. Theodorsson A, Theodorsson E. Estradiol increases brain lesions in the cortex and lateral striatum after transient occlusion of the middle cerebral artery in rats: no effect of ischemia on galanin in the stroke area but decreased levels in the hippocampus. Peptides 2005;26:2257-2264. https://doi.org/10.1016/j.peptides.2005.04.013
  25. Hummon AB, Richmond TA, Verleyen P, Baggerman G, Huybrechts J, Ewing MA, et al. From the genome to the proteome: uncovering peptides in the Apis brain. Science 2006;314:647-649. https://doi.org/10.1126/science.1124128
  26. Li L, Kelley WP, Billimoria CP, Christie AE, Pulver SR, Sweedler JV, et al. Mass spectrometric investigation of the neuropeptide complement and release in the pericardial organs of the crab, Cancer borealis. J Neurochem 2003;87:642-656. https://doi.org/10.1046/j.1471-4159.2003.02031.x
  27. Romanova EV, Roth MJ, Rubakhin SS, Jakubowski JA, Kelley WP, Kirk MD, et al. Identification and characterization of homologues of vertebrate beta-thymosin in the marine mollusk Aplysia californica. J Mass Spectrom 2006;41:1030-1040. https://doi.org/10.1002/jms.1060
  28. Predel R, Wegener C, Russell WK, Tichy SE, Russell DH, Nachman RJ. Peptidomics of CNS-associated neurohemal systems of adult Drosophila melanogaster: a mass spectrometric survey of peptides from individual flies. J Comp Neurol 2004;474:379-392. https://doi.org/10.1002/cne.20145
  29. Sturm RM, Dowell JA, Li L. Rat brain neuropeptidomics: tissue collection, protease inhibition, neuropeptide extraction, and mass spectrometric analysis. Methods Mol Biol 2010;615:217-226.
  30. Li L, Sweedler JV. Peptides in the brain: mass spectrometry-based measurement approaches and challenges. Annu Rev Anal Chem (Palo Alto Calif) 2008;1:451-483. https://doi.org/10.1146/annurev.anchem.1.031207.113053
  31. Che FY, Zhang X, Berezniuk I, Callaway M, Lim J, Fricker LD. Optimization of neuropeptide extraction from the mouse hypothalamus. J Proteome Res 2007;6:4667-4676. https://doi.org/10.1021/pr060690r
  32. Svensson M, Skold K, Svenningsson P, Andren PE. Peptidomics-based discovery of novel neuropeptides. J Proteome Res 2003;2:213-219. https://doi.org/10.1021/pr020010u
  33. Schrader M, Schulz-Knappe P, Fricker LD. Historical perspective of peptidomics. EuPA Open Proteom 2014;3:171-182. https://doi.org/10.1016/j.euprot.2014.02.014
  34. Che FY, Lim J, Pan H, Biswas R, Fricker LD. Quantitative neuropeptidomics of microwave-irradiated mouse brain and pituitary. Mol Cell Proteomics 2005;4:1391-1405. https://doi.org/10.1074/mcp.T500010-MCP200
  35. Theodorsson E, Stenfors C, Mathe AA. Microwave irradiation increases recovery of neuropeptides from brain tissues. Peptides 1990;11:1191-1197. https://doi.org/10.1016/0196-9781(90)90151-T
  36. Dowell JA, Heyden WV, Li L. Rat neuropeptidomics by LC-MS/MS and MALDI-FTMS: Enhanced dissection and extraction techniques coupled with 2D RP-RP HPLC. J Proteome Res 2006;5:3368-3375. https://doi.org/10.1021/pr0603452
  37. Lee JE, Atkins N Jr, Hatcher NG, Zamdborg L, Gillette MU, Sweedler JV, et al. Endogenous peptide discovery of the rat circadian clock: a focused study of the suprachiasmatic nucleus by ultrahigh performance tandem mass spectrometry. Mol Cell Proteomics 2010;9:285-297. https://doi.org/10.1074/mcp.M900362-MCP200
  38. Nylander I, Stenfors C, Tan-No K, Mathe AA, Terenius L. A comparison between microwave irradiation and decapitation: basal levels of dynorphin and enkephalin and the effect of chronic morphine treatment on dynorphin peptides. Neuropeptides 1997;31:357-365. https://doi.org/10.1016/S0143-4179(97)90072-X
  39. Bora A, Annangudi SP, Millet LJ, Rubakhin SS, Forbes AJ, Kelleher NL, et al. Neuropeptidomics of the supraoptic rat nucleus. J Proteome Res 2008;7:4992-5003. https://doi.org/10.1021/pr800394e
  40. Chen R, Jiang X, Conaway MC, Mohtashemi I, Hui L, Viner R, et al. Mass spectral analysis of neuropeptide expression and distribution in the nervous system of the lobster Homarus americanus. J Proteome Res 2010;9:818-832. https://doi.org/10.1021/pr900736t
  41. Jia C, Lietz CB, Ye H, Hui L, Yu Q, Yoo S, et al. A multi-scale strategy for discovery of novel endogenous neuropeptides in the crustacean nervous system. J Proteomics 2013;91:1-12. https://doi.org/10.1016/j.jprot.2013.06.021
  42. Sasaki K, Osaki T, Minamino N. Large-scale identification of endogenous secretory peptides using electron transfer dissociation mass spectrometry. Mol Cell Proteomics 2013;12:700-709. https://doi.org/10.1074/mcp.M112.017400
  43. Hayakawa E, Menschaert G, De Bock PJ, Luyten W, Gevaert K, Baggerman G, et al. Improving the identification rate of endogenous peptides using electron transfer dissociation and collision-induced dissociation. J Proteome Res 2013;12:5410-5421. https://doi.org/10.1021/pr400446z
  44. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS. Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 1999;20:3551-3567. https://doi.org/10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2
  45. Eng JK, McCormack AL, Yates JR. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 1994;5:976-989. https://doi.org/10.1016/1044-0305(94)80016-2
  46. Craig R, Beavis RC. TANDEM: matching proteins with tandem mass spectra. Bioinformatics 2004;20:1466-1467. https://doi.org/10.1093/bioinformatics/bth092
  47. Ma B, Zhang K, Hendrie C, Liang C, Li M, Doherty-Kirby A, et al. PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun Mass Spectrom 2003;17:2337-2342. https://doi.org/10.1002/rcm.1196
  48. Falth M, Skold K, Norrman M, Svensson M, Fenyo D, Andren PE. SwePep, a database designed for endogenous peptides and mass spectrometry. Mol Cell Proteomics 2006;5:998-1005. https://doi.org/10.1074/mcp.M500401-MCP200
  49. Southey BR, Amare A, Zimmerman TA, Rodriguez-Zas SL, Sweedler JV. NeuroPred: a tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides. Nucleic Acids Res 2006;34:W267-W272. https://doi.org/10.1093/nar/gkl161
  50. Romanova EV, Sweedler JV. Peptidomics for the discovery and characterization of neuropeptides and hormones. Trends Pharmacol Sci 2015;36:579-586. https://doi.org/10.1016/j.tips.2015.05.009
  51. Romanova EV, Dowd SE, Sweedler JV. Quantitation of endogenous peptides using mass spectrometry based methods. Curr Opin Chem Biol 2013;17:801-808. https://doi.org/10.1016/j.cbpa.2013.05.030
  52. Hou X, Xie F, Sweedler JV. Relative quantitation of neuropeptides over a thousand-fold concentration range. J Am Soc Mass Spectrom 2012;23:2083-2093. https://doi.org/10.1007/s13361-012-0481-0
  53. Che FY, Vathy I, Fricker LD. Quantitative peptidomics in mice: effect of cocaine treatment. J Mol Neurosci 2006;28:265-275. https://doi.org/10.1385/JMN:28:3:265
  54. Che FY, Yuan Q, Kalinina E, Fricker LD. Peptidomics of Cpe fat/fat mouse hypothalamus: effect of food deprivation and exercise on peptide levels. J Biol Chem 2005;280:4451-4461. https://doi.org/10.1074/jbc.M411178200
  55. Decaillot FM, Che FY, Fricker LD, Devi LA. Peptidomics of Cpefat/fat mouse hypothalamus and striatum: effect of chronic morphine administration. J Mol Neurosci 2006;28:277-284. https://doi.org/10.1385/JMN:28:3:277
  56. Wardman JH, Zhang X, Gagnon S, Castro LM, Zhu X, Steiner DF, et al. Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics. J Neurochem 2010;114:215-225.
  57. Zhang X, Pan H, Peng B, Steiner DF, Pintar JE, Fricker LD. Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis. J Neurochem 2010;112:1168-1179. https://doi.org/10.1111/j.1471-4159.2009.06530.x
  58. Lee JE, Zamdborg L, Southey BR, Atkins N Jr, Mitchell JW, Li M, et al. Quantitative peptidomics for discovery of circadian-related peptides from the rat suprachiasmatic nucleus. J Proteome Res 2013;12:585-593. https://doi.org/10.1021/pr300605p
  59. Southey BR, Lee JE, Zamdborg L, Atkins N Jr, Mitchell JW, Li M, et al. Comparing label-free quantitative peptidomics approaches to characterize diurnal variation of peptides in the rat suprachiasmatic nucleus. Anal Chem 2014;86:443-452. https://doi.org/10.1021/ac4023378
  60. Scholz B, Alm H, Mattsson A, Nilsson A, Kultima K, Savitski MM, et al. Neuropeptidomic analysis of the embryonic Japanese quail diencephalon. BMC Dev Biol 2010;10:30. https://doi.org/10.1186/1471-213X-10-30
  61. Rossbach U, Nilsson A, Falth M, Kultima K, Zhou Q, Hallberg M, et al. A quantitative peptidomic analysis of peptides related to the endogenous opioid and tachykinin systems in nucleus accumbens of rats following naloxone-precipitated morphine withdrawal. J Proteome Res 2009;8:1091-1098. https://doi.org/10.1021/pr800669g
  62. Romanova EV, Lee JE, Kelleher NL, Sweedler JV, Gulley JM. Comparative peptidomics analysis of neural adaptations in rats repeatedly exposed to amphetamine. J Neurochem 2012;123:276-287. https://doi.org/10.1111/j.1471-4159.2012.07912.x
  63. Romanova EV, Lee JE, Kelleher NL, Sweedler JV, Gulley JM. Mass spectrometry screening reveals peptides modulated differentially in the medial prefrontal cortex of rats with disparate initial sensitivity to cocaine. AAPS J 2010;12:443-454. https://doi.org/10.1208/s12248-010-9204-2