Skip to main content
Top
Published in: Translational Stroke Research 5/2019

01-10-2019 | Original Article

From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke

Authors: Hailong Song, Hui Zhou, Zhe Qu, Jie Hou, Weilong Chen, Weiwu Cai, Qiong Cheng, Dennis Y. Chuang, Shanyan Chen, Shuwei Li, Jilong Li, Jianlin Cheng, C. Michael Greenlief, Yuan Lu, Agnes Simonyi, Grace Y. Sun, Chenghan Wu, Jiankun Cui, Zezong Gu

Published in: Translational Stroke Research | Issue 5/2019

Login to get access

Abstract

Ischemic stroke is a devastating neurological disease that can cause permanent brain damage, but to date, few biomarkers are available to reliably assess the severity of injury during acute onset. In this study, quantitative proteomic analysis of ischemic mouse brain detected the increase in expression levels of clusterin (CLU) and cystatin C (CST3). Since CLU is a secretary protein, serum samples (n = 70) were obtained from acute ischemic stroke (AIS) patients within 24 h of stroke onset and together with 70 matched health controls. Analysis of CLU levels indicated significantly higher levels in AIS patients than healthy controls (14.91 ± 4.03 vs. 12.79 ± 2.22 ng/L; P = 0.0004). Analysis of serum CST3 also showed significant increase in AIS patients as compared with healthy controls (0.90 ± 0.19 vs. 0.84 ± 0.12 ng/L; P = 0.0064). The serum values of CLU were also positively correlated with the NIH Stroke Scale (NIHSS) scores, the time interval after stroke onset, as well as major stroke risk factors associated with lipid profile. These data demonstrate that elevated levels of serum CLU and CST3 are independently associated with AIS and may serve as peripheral biomarkers to aid clinical assessment of AIS and its severity. This pilot study thus contributes to progress toward preclinical proteomic screening by using animal models and allows translation of results from bench to bedside.
Appendix
Available only for authorised users
Literature
12.
go back to reference Swan AL, Mobasheri A, Allaway D, Liddell S, Bacardit J. Application of machine learning to proteomics data: classification and biomarker identification in postgenomics biology. OMICS. 2013;17(12):595–610.CrossRefPubMedPubMedCentral Swan AL, Mobasheri A, Allaway D, Liddell S, Bacardit J. Application of machine learning to proteomics data: classification and biomarker identification in postgenomics biology. OMICS. 2013;17(12):595–610.CrossRefPubMedPubMedCentral
17.
24.
go back to reference Chuang DY, Cui J, Simonyi A, Engel VA, Chen S, Fritsche KL et al. Dietary Sutherlandia and elderberry mitigate cerebral ischemia-induced neuronal damage and attenuate p47phox and phospho-ERK1/2 expression in microglial cells. ASN Neuro. 2014;6(6). https://doi.org/10.1177/1759091414554946. Chuang DY, Cui J, Simonyi A, Engel VA, Chen S, Fritsche KL et al. Dietary Sutherlandia and elderberry mitigate cerebral ischemia-induced neuronal damage and attenuate p47phox and phospho-ERK1/2 expression in microglial cells. ASN Neuro. 2014;6(6). https://​doi.​org/​10.​1177/​1759091414554946​.
27.
go back to reference Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581–641.CrossRefPubMed Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581–641.CrossRefPubMed
28.
go back to reference Lyden PD, Lu M, Levine SR, Brott TG, Broderick J, Group NrSS. A modified National Institutes of Health Stroke Scale for use in stroke clinical trials: preliminary reliability and validity. Stroke. 2001;32(6):1310–7.CrossRefPubMed Lyden PD, Lu M, Levine SR, Brott TG, Broderick J, Group NrSS. A modified National Institutes of Health Stroke Scale for use in stroke clinical trials: preliminary reliability and validity. Stroke. 2001;32(6):1310–7.CrossRefPubMed
30.
go back to reference Shimizu-Tokiwa A, Kobata M, Io H, Kobayashi N, Shou I, Funabiki K, et al. Serum cystatin C is a more sensitive marker of glomerular function than serum creatinine. Nephron. 2002;92(1):224–6.CrossRefPubMed Shimizu-Tokiwa A, Kobata M, Io H, Kobayashi N, Shou I, Funabiki K, et al. Serum cystatin C is a more sensitive marker of glomerular function than serum creatinine. Nephron. 2002;92(1):224–6.CrossRefPubMed
37.
go back to reference Jauch EC WK, Carrozzella J. Proteomic analyses demonstrates ultra-early elevations of inflammation-sensitive plasma proteins following ischemic stroke. 5th World Stroke Congress, Vancouver BC, Canada. 2004. Jauch EC WK, Carrozzella J. Proteomic analyses demonstrates ultra-early elevations of inflammation-sensitive plasma proteins following ischemic stroke. 5th World Stroke Congress, Vancouver BC, Canada. 2004.
39.
go back to reference Chow SL, Maisel AS, Anand I, Bozkurt B, De Boer RA, Felker GM, et al. Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association. Circulation. 2017;135(22):e1054–e91.CrossRefPubMed Chow SL, Maisel AS, Anand I, Bozkurt B, De Boer RA, Felker GM, et al. Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association. Circulation. 2017;135(22):e1054–e91.CrossRefPubMed
49.
go back to reference Turk V, Turk B, Guncar G, Turk D, Kos J. Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzym Regul. 2002;42:285–303.CrossRef Turk V, Turk B, Guncar G, Turk D, Kos J. Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzym Regul. 2002;42:285–303.CrossRef
51.
go back to reference Hakansson K, Huh C, Grubb A, Karlsson S, Abrahamson M. Mouse and rat cystatin C: Escherichia coli production, characterization and tissue distribution. Comp Biochem Physiol B Biochem Mol Biol. 1996;114(3):303–11.CrossRefPubMed Hakansson K, Huh C, Grubb A, Karlsson S, Abrahamson M. Mouse and rat cystatin C: Escherichia coli production, characterization and tissue distribution. Comp Biochem Physiol B Biochem Mol Biol. 1996;114(3):303–11.CrossRefPubMed
Metadata
Title
From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke
Authors
Hailong Song
Hui Zhou
Zhe Qu
Jie Hou
Weilong Chen
Weiwu Cai
Qiong Cheng
Dennis Y. Chuang
Shanyan Chen
Shuwei Li
Jilong Li
Jianlin Cheng
C. Michael Greenlief
Yuan Lu
Agnes Simonyi
Grace Y. Sun
Chenghan Wu
Jiankun Cui
Zezong Gu
Publication date
01-10-2019
Publisher
Springer US
Published in
Translational Stroke Research / Issue 5/2019
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-018-0675-2

Other articles of this Issue 5/2019

Translational Stroke Research 5/2019 Go to the issue