Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.727
Index Copernicus  – 166.39
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 8, August, p. 1075–1080

doi: 10.17219/acem/70441

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Pathophysiological implications of actin-free Gc-globulin concentration changes in blood plasma and cerebrospinal fluid collected from patients with Alzheimer’s disease and other neurological disorders

Alina Kułakowska1,D, Joanna Tarasiuk1,D, Katarzyna Kapica-Topczewska1,D, Monika Chorąży1,D, Robert Pogorzelski1,D, Agnieszka Kulczyńska-Przybik2,A, Barbara Mroczko2,A, Robert Bucki3,D

1 Department of Neurology, Medical University of Białystok, Poland

2 Department of Neurodegeneration Diagnostics, Medical University of Białystok, Poland

3 Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, Poland

Abstract

Background. The extracellular actin scavenging system (EASS) is composed of plasma Gc-globulin and gelsolin, and is responsible for the elimination of toxic actin from the bloodstream.
Objectives. In this study, we assessed the actin-free Gc-globulin concentrations in blood plasma and cerebrospinal fluid (CSF) obtained from subjects with neurodegenerative and inflammatory diseases of the central nervous system (CNS) as well as in a control group.
Material and Methods. Using an enzyme-linked immunosorbent assay (ELISA), we measured the actinfree Gc-globulin concentrations in blood plasma and CSF obtained from subjects diagnosed with Alzheimer’s disease (AD) (n = 20), amyotrophic lateral sclerosis (ALS) (n = 12), multiple sclerosis (MS) (n = 42), tick-borne encephalitis (TBE) (n = 12), and from a control group (n = 20).
Results. The concentrations of free Gc-globulin in plasma collected from patients diagnosed with AD (509.6 ±87.6 mg/L) and ALS (455.5 ±99.8 mg/L) did not differ significantly between each other, but were significantly higher compared to the reference group (311.7 ±87.5 mg/L) (p < 0.001 and p < 0.006, respectively) as well as to MS (310.8 ±66.6 mg/L) (p < 0.001 and p < 0.001, respectively) and TBE (256.7 ±76 mg/L) (p < 0.001 and p < 0.003, respectively). In CSF collected from patients diagnosed with AD and ALS, the concentrations of free Gc-globulin were 2.6 ±1.1 mg/L and 2.7 ±1.9 mg/L, respectively. They did not differ significantly between each other and were significantly higher compared to the reference group (1.5 ±0.9 mg/L) (p < 0.005 and p < 0.041, respectively). Interestingly, in patients with AD, significantly higher values of Gcglobulin were detected compared to multiple sclerosis patients (1.7 ±0.9 mg/L) (p < 0.013).
Conclusion. Higher concentrations of free Gc-globulin in blood plasma and CSF collected from patients suffering from neurodegenerative diseases may indicate a potential role of this protein in their pathogenesis, and represent a potential tool for the diagnosis of CNS diseases.

Key words

Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, tick-borne encephalitis, Gc-globulin

References (39)

  1. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab. 2000;11:320–327.
  2. Meier U, Gressner O, Lammert F, Gressner AM. Gc-globulin: Roles in response to injury. Clin Chem. 2006;52:1247–1253.
  3. Kułakowska A, Zajkowska JM, Ciccarelli NJ, Mroczko B, Drozdowski W, Bucki R. Depletion of plasma gelsolin in patients with tick-borne encephalitis and Lyme neuroborreliosis. Neurodegener Dis. 2011;8:375–380.
  4. Kułakowska A, Ciccarelli NJ, Wen Q, et al. Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis. BMC Neurol. 2010;10:107.
  5. Schiødt FV, Bangert K, Shakil AO, et al. Predictive value of actin-free Gc-globulin in acute liver failure. Liver Transpl. 2007;13:1324–1329.
  6. Bagchi A, Kumar S, Ray PC, Das BC, Gumma PK, Kar P. Predictive value of serum actin-free Gc-globulin for complications and outcome in acute liver failure. J Viral Hepat. 2015;22:192–200.
  7. Łukaszewicz-Zajac M, Mroczko B, Kułakowska A, Szmitkowski M. The significance of Gc-globulin in clinical practice [in Polish]. Postepy Hig Med Dosw. 2008;62:625–631.
  8. Bredesen DE, Rao RV, Mehlen P. Cell death in the nervous system. Nature. 2006;443:796–802.
  9. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734–746.
  10. Croisile B, Auriacombe S, Etcharry-Bouyx F, Vercelletto M; NIoA & Alzheimer’s Association. The new 2011 recommendations of the National Institute on Aging and the Alzheimer’s Association on diagnostic guidelines for Alzheimer’s disease: Preclinical stages, mild cognitive impairment, and dementia [in French]. Rev Neurol (Paris). 2012;168:471–482.
  11. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.
  12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology. 1983;3:1444–1452.
  13. Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Disease. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293–299.
  14. Chieia MA, Oliveira AS, Silva HC, Gabbai AA. Amyotrophic lateral sclerosis: Considerations on diagnostic criteria. Arq Neuropsiquiatr. 2010;68:837–842.
  15. Gressner OA, Schifflers MC, Kim P, Heuts L, Lahme B, Gressner AM. Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: Relationship to S-100B levels and blood-brain barrier function. Clin Chim Acta. 2009;400:86–90.
  16. Zhang J, Sokal I, Peskind ER, et al. CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol. 2008;129:526–529.
  17. Agdeppa ED, Kepe V, Liu J, et al. Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci. 2001;21:RC189.
  18. Ashford JW, Shih WJ, Coupal J, et al. Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer’s disease. J Nucl Med. 2000;41:57–64.
  19. Gomme PT, Bertolini J. Therapeutic potential of vitamin D-binding protein. Trends Biotechnol. 2004;22:340–345.
  20. Dahl B, Schiødt FV, Ott P, et al. Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury. Crit Care Med. 2003;31:152–156.
  21. Antequera D, Vargas T, Ugalde C, et al. Cytoplasmic gelsolin increases mitochondrial activity and reduces Abeta burden in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2009;36:42–50.
  22. Bucki R, Kulakowska A, Byfield FJ, et al. Plasma gelsolin modulates cellular response to sphingosine 1-phosphate. Am J Physiol Cell Physiol. 2010;299:C1516–1523.
  23. Bucki R, Byfield FJ, Kulakowska A, et al. Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components. J Immunol. 2008;181:4936–4944.
  24. Bucki R, Georges PC, Espinassous Q, et al. Inactivation of endotoxin by human plasma gelsolin. Biochemistry. 2005;44:9590–9597.
  25. Bucki R, Janmey PA. Interaction of the gelsolin-derived antibacterial PBP 10 peptide with lipid bilayers and cell membranes. Antimicrob Agents Chemother. 2006;50:2932–2940.
  26. Lukiw WJ, Bazan NG. Survival signalling in Alzheimer’s disease. Biochem Soc Trans. 2006;34:1277–1282.
  27. Takasugi N, Sasaki T, Ebinuma I, et al. FTY720/fingolimod, a sphingosine analogue, reduces amyloid-β production in neurons. PLoS One. 2013;8:e64050.
  28. Takasugi N, Sasaki T, Suzuki K, et al. BACE1 activity is modulated by cell-associated sphingosine-1-phosphate. J Neurosci. 2011;31:6850–6857.
  29. Fukumoto K, Mizoguchi H, Takeuchi H, et al. Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment. Behav Brain Res. 2014;268:88–93.
  30. Brunkhorst R, Vutukuri R, Pfeilschifter W. Fingolimod for the treatment of neurological diseases-state of play and future perspectives. Front Cell Neurosci. 2014;8:283.
  31. Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2011;93:1–12.
  32. Trapp BD, Nave KA. Multiple sclerosis: An immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247–269.
  33. Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535–561.
  34. Micu I, Jiang Q, Coderre E, et al. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature. 2006;439:988–992.
  35. Bennett JL, Stüve O. Update on inflammation, neurodegeneration, and immunoregulation in multiple sclerosis: Therapeutic implications. Clin Neuropharmacol. 2009;32:121–132.
  36. Gelpi E, Preusser M, Laggner U, et al. Inflammatory response in human tick-borne encephalitis: Analysis of postmortem brain tissue. J Neurovirol. 2006;12:322–327.
  37. Holick MF. Vitamin D status: Measurement, interpretation, and clinical application. Ann Epidemiol. 2009;19:73–78.
  38. Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: Definition, prevalence, consequences, and correction. Endocrinol Metab Clin North Am. 2010;39:287–301.
  39. Littlejohns TJ, Henley WE, Lang IA, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83:920–928.