TY - JOUR
T1 - Quantitative proteomics for identifying biomarkers for rabies
AU - Venugopal, Abhilash K.
AU - Ghantasala, S. Sameer Kumar
AU - Selvan, Lakshmi Dhevi N.
AU - Mahadevan, Anita
AU - Renuse, Santosh
AU - Kumar, Praveen
AU - Pawar, Harsh
AU - Sahasrabhuddhe, Nandini A.
AU - Suja, Mooriyath S.
AU - Ramachandra, Yarappa L.
AU - Prasad, Thottethodi S.Keshava
AU - Madhusudhana, Shampur N.
AU - Harsha, H. C.
AU - Chaerkady, Raghothama
AU - Satishchandra, Parthasarathy
AU - Pandey, Akhilesh
AU - Shankar, Susarla K.
N1 - Funding Information:
We thank the Department of Biotechnology (DBT), Government of India for research support on Neuroproteomics for Proteomic Investigation of Neurological Disorders” to the Institute of Bioinformatics and National Institute of Mental Health and Neurosciences. Harsha Gowda is a Wellcome Trust-DBT India Alliance Early Career Fellow. T.S. Keshava Prasad is supported by a research grant on “Development of Infrastructure and a Computational Framework for Analysis of Proteomic Data” from DBT. Harsh Pawar and Nandini A. Sahasrabuddhe are recipients of a senior research fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. Santosh Renuse is recipient of a senior research fellowship from the University Grants Commission (UGC), Government of India. Akhilesh Pandey is supported in part by a grant S10RR023025 from the High End Instrumentation Program of the National Institutes of Health and an NIH roadmap grant for Technology Centers of Networks and Pathways (U54RR020839). Human brain tissues for the study were obtained from the Human Brain Tissue Repository, a National Research Facility in the Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Secretarial assistance of Mrs. Manjula Madan is acknowledged.
PY - 2013
Y1 - 2013
N2 - Introduction: Rabies is a fatal acute viral disease of the central nervous system, which is a serious public health problem in Asian and African countries. Based on the clinical presentation, rabies can be classified into encephalitic (furious) or paralytic (numb) rabies. Early diagnosis of this disease is particularly important as rabies is invariably fatal if adequate post exposure prophylaxis is not administered immediately following the bite. Methods: In this study, we carried out a quantitative proteomic analysis of the human brain tissue from cases of encephalitic and paralytic rabies along with normal human brain tissues using an 8-plex isobaric tags for relative and absolute quantification (iTRAQ) strategy. Results and conclusion: We identified 402 proteins, of which a number of proteins were differentially expressed between encephalitic and paralytic rabies, including several novel proteins. The differentially expressed molecules included karyopherin alpha 4 (KPNA4), which was overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A), which was upregulated in paralytic rabies group and glutamate ammonia ligase (GLUL), which was overexpressed in paralytic as well as encephalitic rabies. We validated two of the upregulated molecules, GLUL and CAMK2A, by dot blot assays and further validated CAMK2A by immunohistochemistry. These molecules need to be further investigated in body fluids such as cerebrospinal fluid in a larger cohort of rabies cases to determine their potential use as antemortem diagnostic biomarkers in rabies. This is the first study to systematically profile clinical subtypes of human rabies using an iTRAQ quantitative proteomics approach.
AB - Introduction: Rabies is a fatal acute viral disease of the central nervous system, which is a serious public health problem in Asian and African countries. Based on the clinical presentation, rabies can be classified into encephalitic (furious) or paralytic (numb) rabies. Early diagnosis of this disease is particularly important as rabies is invariably fatal if adequate post exposure prophylaxis is not administered immediately following the bite. Methods: In this study, we carried out a quantitative proteomic analysis of the human brain tissue from cases of encephalitic and paralytic rabies along with normal human brain tissues using an 8-plex isobaric tags for relative and absolute quantification (iTRAQ) strategy. Results and conclusion: We identified 402 proteins, of which a number of proteins were differentially expressed between encephalitic and paralytic rabies, including several novel proteins. The differentially expressed molecules included karyopherin alpha 4 (KPNA4), which was overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A), which was upregulated in paralytic rabies group and glutamate ammonia ligase (GLUL), which was overexpressed in paralytic as well as encephalitic rabies. We validated two of the upregulated molecules, GLUL and CAMK2A, by dot blot assays and further validated CAMK2A by immunohistochemistry. These molecules need to be further investigated in body fluids such as cerebrospinal fluid in a larger cohort of rabies cases to determine their potential use as antemortem diagnostic biomarkers in rabies. This is the first study to systematically profile clinical subtypes of human rabies using an iTRAQ quantitative proteomics approach.
KW - Hierarchical cluster
KW - Liquid chromatography
KW - Mass spectrometry
KW - Post exposure vaccination
KW - Spectrum mill
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U2 - 10.1186/1559-0275-10-3
DO - 10.1186/1559-0275-10-3
M3 - Article
C2 - 23521751
AN - SCOPUS:84890074439
SN - 1542-6416
VL - 10
JO - Clinical Proteomics
JF - Clinical Proteomics
IS - 1
M1 - 3
ER -