본문 바로가기
KERD
논문KCI 등재

Proteomic Identification of Proteins Suggestive of Immune-Mediated Response or Neuronal Degeneration in Serum of Achalasia Patients

1

조회

0

다운로드

2

인용

0

참고문헌

초록

Background/Aims: The primary pathophysiologic abnormality in achalasia is known to be a loss of inhibitory myenteric ganglion cells, which may result from an immune-mediated response or neuronal degeneration. The aim of this study was to identify proteins suggestive of an immune-mediated response or neuronal degeneration in the serum of achalasia patients using a proteomic analysis. Methods: Blood samples were collected from five symptomatic achalasia patients and five sex- and age-matched healthy controls. Serum proteomic analysis was conducted, and the protein spots were identified using matrix-assisted laser desorption ionization/time-of-flight and a proteomics analyzer. The serum level of C3 was measured by enzyme-linked immunosorbent assay in nine patients with achalasia and 18 sex- and age-matched healthy controls. Results: Of the 658 matched protein spots,28 spots were up-regulated over 2-fold in the serum from achalasia patients compared with that from controls. The upregulated proteins included complement C4B5, complement C3, cyclin-dependent kinase 5, transthyretin, and alpha 2macroglobulin. The serum levels of C3 in achalasia patients were significantly higher than those of controls. Conclusions:The serum proteomic analysis of achalasia patients suggests an immune-mediated response or neuronal degeneration. Further validation studies in larger samples and the esophageal tissue of achalasia patients are required.

Abstract

Background/Aims: The primary pathophysiologic abnormality in achalasia is known to be a loss of inhibitory myenteric ganglion cells, which may result from an immune-mediated response or neuronal degeneration. The aim of this study was to identify proteins suggestive of an immune-mediated response or neuronal degeneration in the serum of achalasia patients using a proteomic analysis. Methods: Blood samples were collected from five symptomatic achalasia patients and five sex- and age-matched healthy controls. Serum proteomic analysis was conducted, and the protein spots were identified using matrix-assisted laser desorption ionization/time-of-flight and a proteomics analyzer. The serum level of C3 was measured by enzyme-linked immunosorbent assay in nine patients with achalasia and 18 sex- and age-matched healthy controls. Results: Of the 658 matched protein spots,28 spots were up-regulated over 2-fold in the serum from achalasia patients compared with that from controls. The upregulated proteins included complement C4B5, complement C3, cyclin-dependent kinase 5, transthyretin, and alpha 2macroglobulin. The serum levels of C3 in achalasia patients were significantly higher than those of controls. Conclusions:The serum proteomic analysis of achalasia patients suggests an immune-mediated response or neuronal degeneration. Further validation studies in larger samples and the esophageal tissue of achalasia patients are required.

참고문헌 (25)

  1. Katz PO, "Apparent complete lower esophageal sphincter relaxation in achalasia", Gastroenterology, 90, pp.978~983 (1986)
  2. Park W, "Etiology and pathogenesis of achalasia: the current understanding", Am J Gastroenterol, 100, pp.1404~1414 (2005)
  3. Wilkins MR, "From proteins to proteomes: large scale protein identification by two-dimensional electrophoresis and amino acid analysis", Biotechnology (NY), 14, pp.61~65 (1996)
  4. "Biomarkers and surrogate endpoints: preferred definitions and conceptual framework", Clin Pharmacol Ther, 69, pp.89~95 (2001)
  5. Sultana R, "Redox proteomics identification of oxidized proteins in Alzheimer’s disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD", Neurobiol Aging, 27, pp.1564~1576 (2006)
  6. Goldblum JR, "Achalasia. A morphologic study of 42 resected specimens", Am J Surg Pathol, 18, pp.327~337 (1994)
  7. Goldblum JR, "Histopathologic features in esophagomyotomy specimens from patients with achalasia", Gastroenterology, 111, pp.648~654 (1996)
  8. Frieling T, "Family occurrence of achalasia and diffuse spasm of the oesophagus", Gut, 29, pp.1595~1602 (1988)
  9. Robertson CS, "Varicella-zoster virus DNA in the oesophageal myenteric plexus in achalasia", Gut, 34, pp.299~302 (1993)
  10. Parrilla P, "Reversible achalasia-like motor pattern of esophageal body secondary to postoperative stricture of gastroesophageal junction", Dig Dis Sci, 37, pp.1781~1784 (1992)
  11. Qualman SJ, "Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson’s disease", Gastroenterology, 87, pp.848~856 (1984)
  12. Murphy MS, "Achalasia of the cardia associated with hereditary cerebellar ataxia", Am J Gastroenterol, 84, pp.1329~1330 (1989)
  13. Tumani H, "2D DIGE of the cerebrospinal fluid proteome in neurological diseases", Expert Rev Proteomics, 7, pp.29~38 (2010)
  14. Ando Y, "Novel methods for detecting amyloidogenic proteins in transthyretin related amyloidosis", Front Biosci, 13, pp.5548~5558 (2008)
  15. Hou X, "Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegeneration", FEBS J, 274, pp.1637~1650 (2007)
  16. Walport MJ, "Complement. First of two parts", N Engl J Med, 344, pp.1058~1066 (2001)
  17. Morgan BP, "Expression of complement in the brain: role in health and disease", Immunol Today, 17, pp.461~466 (1996)
  18. Coleman RM, "Fundamental immunology" (1989), Brown Publishers
  19. Storch WB, "Complement components and terminal complement complex in oesophageal smooth muscle of patients with achalasia", Cell Mol Biol (Noisy-le-grand), 48, pp.247~252 (2002)
  20. Kesavapany S, "Neuronal cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the Cdk5 inhibitory peptide", Biochim Biophys Acta, 1697, pp.143~153 (2004)
  21. Maccioni RB, "The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer’s pathology", Eur J Biochem, 268, pp.1518~1527 (2001)
  22. Honjyo Y, "Immunohistochemical localization of CDK5 activator p39 in the rat brain", Neuroreport, 10, pp.3375~3379 (1999)
  23. Sottrup-Jensen L, "The alpha-macroglobulin bait region. Sequence diversity and localization of cleavage sites for proteinases in five mammalian alpha-macroglobulins", J Biol Chem, 264, pp.15781~15789 (1989)
  24. Mocchegiani E, "Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and immunosenescence", Exp Gerontol, 41, pp.1094~1107 (2006)
  25. Kovacs DM, "alpha2-macroglobulin in late-onset Alzheimer’s disease", Exp Gerontol, 35, pp.473~479 (2000)

관련 논문AI추천

이 간행물의 다른 논문 (19건)