Serum Carnosine Dipeptidase 1 and Ubiquitin C - Terminal Hydrolase L1 as Markers of Brain Damage in Patients After Carotid Endarterectomy

Year 2016, Volume: 2 Issue: 3, 132 - 137, 01.07.2016

Marek Ilzecki Joanna Ilzecka Stanislaw Przywara Aneta Grabarska Piotr Terlecki Andrzej Stepulak Shawn Dave Tomasz Zubilewicz

https://doi.org/10.5455/umj.20160713014033

Abstract

Background: Carotid endarterectomy CEA is the recommended surgical procedure in the prevention of ischemic stroke. However, this procedure may lead to vascular neurological complications. The aim of the study was to measure serum carnosine dipeptidase 1 CNDP1 and ubiquitin C - terminal hydrolase L1 UCHL1 as markers of brain damagein patients that underwent CEA due to high-grade internal carotid artery stenosis. Method: This study included in 25 patients. Blood samples were taken from the antecubital vein at three different intervals within a 24 h period prior to CEA, 12 h following surgery, and 48 h after surgery . Serum CNDP1 and UCHL1 levels were measured by a commercially available enzyme-linked immunosorbent assay ELISA . Results: The study showed that serum CNDP1 and UCHL1 levels were significantly decreased 12 h after CEA when compared to level before the surgery. Furthermore, these enzymes levels were normalized 48 h after CEA. Conclusion: Data from our study showed that CEA significantly affects serum CNDP1 and UCHL1 levels. Moreover, these enzyme levels seems to reflect a brain ischemia resulting from severe internal carotid artery stenosis in patients undergoing CEA.

Keywords

Carnosine dipeptidase 1, carotid endarterectomy, ischemic stroke, ubiquitin C - terminal hydrolase L1

References

• 1. Jennum P, Iversen HK, Ibsen R, Kjellberg J. Cost of stroke: a controlled national study evaluating societal effects on patients and partners. BMC Health Serv Res 2015; 15(1):466.
• 2. Naylor AR. Time is brain: an update. Expert Rev Cardiovasc Ther 2015;13(10):1111-26.
• 3. Gupta N, Corriere MA, Dodson TF, Chaikof EL, Beaulieu RJ, Reeves JG et al. The incidence of microemboli to the brain is less with endarterectomy than percutaneous revascularization with distal filters or flow reversal. J Vasc Surg 2011;53:316-22.
• 4. Backhaus R, Boy S, Fuchs K, Ulrich B, Schuierer G, Schlachetzki F. Hyperperfusion syndrome after MCA embo lectomy; a rare complication? Am J Case Rep 2013;14:513-7
• 5. Ballesteros-Pomar M, Alonso-Argüeso G, Tejada-García J, Vaquero-Morillo F. Cerebral hyperperfusion syndrome in carotid revascularization surgery.Rev Neurol 2012;55(8):490-8.
• 6. Capoccia L, Sbarigia E, et al. Contralateral occlusion increases the risk of neurological complications associated with carotid endarterectomy. Int J Vasc Med 2015;2015:942146.
• 7. Wassif WS, Sherwood RA, Amir A, Idowu B, Summers B, Leigh N. Serum carnosinase activities in central nervous system disorders. Clin Chim Acta 1994;225(1):57-64.
• 8. Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer’s Disease. PLoS One 2011; 6:e16032.
• 9. Gautam P, Nair SC, Gupta MK, Sharma R, Polisetty RV, Uppin MS et al. Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis. PLoS One 2012;7:e46153.
• 10.Kabuta T, Mitsui T, Takahashi M, Fujiwara Y, Kabuta C, Konya C et al. Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation independently of its hydrolase activity. J Biol Chem 2013;288(18):12615-26.
• 11. Tongaonkar P, Chen L, Lambertson D, Madura K. Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome. Mol Cell Biol 2000; 20:4691-8.
• 12.Day IN, Thompson RJ. UCHL1 (PGP 9.5): Neuronal biomarker and ubiquitin system protein. Prog Neurobiol 2010;90(3):327.
• 13. Liu MC, Akinyi L, Scharf D, Mo J, Larner SF, Muller U et al. Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic traumatic brain injury in rats. Eur J Neurosci 2010;31:722-32.
• 14. Lewis SB, Wolper R, Chi YY. Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage. J Neurosci Res 2010;88(7):1475-84.
• 15. Setsuie R, Wada K. The functions of UCH-L1 and its relation to neurodegenerative diseases.Neurochem Int 2007;51(2):105-1.
• 16.Rasmussen LS, Christiansen M, Johnsen J, Grønholdt ML, Moller JT. Subtle brain damage cannot be detected by measuring neuron-specific enolase and S-100beta protein after carotid endarterectomy. J Cardiothorac Vasc Anesth 2000;14(2):166-70.
• 17.Brightwell RE, Sherwood RA, Athanasiou T. The neurological morbidity of carotid revascularization: using markers of cellular brain injury to compare CEA and CAS. Eur J Vasc Endovasc Surg 2007;34:552-60.
• 18.Bellia F, Vecchio G, Rizzarelli E. Carnosinases, their substrates and diseases. Molecules 2014;19(2):2299-329.
• 19.Holdenrieder S, Lütjohann D, Geiger S. Does brain specific 24S-hydroxycholesterol in plasma indicate the disruption of the blood-brain barrier in patients with ischemic stroke? Neurosci Lett 2004;368:201–4.
• 20.Butterworth RJ, Wassif W et al. Serumneuron-specific enolase, carnosinase, and their ratio in acute stroke: an enzymatic test for predicting outcome? Stroke 1996; 27:2064–8.
• 21.Boldyrev AA, Aldini G, Derave W. Physiology and patho physiology of carnosine. Physiol Rev2013;93:1803-45.
• 22.Rajanikant GK, Zemke D, Senut MC, Frenkel MB, Chen AF. Carnosine is neuroprotective against permanent focal cerebral ischemia in mice. Stroke 2007;38(11):3023-31.
• 23.Bellia F, Vecchio G, Cuzzocrea S, Calabrese V, Rizzarelli E. Neuroprotective features of carnosine in oxidative driven diseases. Mol Aspects Med 2011;32(4-6):258-66.
• 24.Pahari DR, Gu YJ, van Oeveren W, El-Essawi A, Harringer W, Brouwer RM. Effect of minimized perfusion circuit on brain injury markers carnosinase and brain-type fatty binding protein in coronary artery bypass grafting patients. Artif Organs 2013;37:128-35.
• 25.Aldini G, Orioli M, Rossoni G, et al. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J Cell Mol Med 2011;15:1339-54.
• 26. Everaert I, Taes Y, De Heer E, et al. Low plasma carnosinase activity promotes carno sinemia after carnosine ingestion in humans. Am J Physiol Renal Physiol 2012;302:1537-44.
• 27. Siman R, Roberts VL, McNeil E, Dang A, Bavaria JE, Ramchandren S, McGarvey M. Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest. Brain Res 2008;1213:1-11.
• 28.Ringger NC, Giguère S, Morresey PR, Yang C, Shaw G. Biomarkers of brain injury in foals with hypoxic-ischemic encephalopathy. J Vet Intern Med 2011;25(1):132-7.
• 29.Douglas-Escobar M, Yang C, Bennett J, Shuster J, Theriaque D et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy.Pediatr Res 2010;68(6):531.
• 30.Roche S, D'Ippolito G, Gomez LA, Bouckenooghe T, Lehmann S, Montero-Menei CN, et al. Comparative analysis of protein expression of 3 stem cell populations: models of cytokine delivery system in vivo. Int J Pharm 2013;440(1):72-82.
• 31.Demyanenko SV, Panchenko SN, Uzdensky AB. Expression of neuronal and signaling proteins in penumbra around a photothrombotic infarction core in rat cerebral cortex. Biochemistry (Mosc) 2015;80(6):790-9.
• 32.Peng Z, Li J, Li Y, Yang X, Feng S, Han S. Downregulation of miR-181b in mouse brain following ischemic stroke induces neuroprotection against ischemic injury through targeting heat shock protein A5 and ubiquitin carboxyl-terminal hydrolase isozyme L1. J Neurosci Res 2013;91(10):1349-62