Quantitative proteomics for identifying biomarkers for Rabies

Clinical Proteomics

Susarla K Shankar⁴  Akhilesh Pandey³  Parthasarathy Satishchandra⁷  Raghothama Chaerkady⁸  Harsha HC⁸  Shampur N Madhusudhana¹  Thottethodi S Keshava Prasad²  Yarappa L Ramachandra⁹  Mooriyath S Suja⁴  Nandini A Sahasrabhuddhe⁵  Harsh Pawar^1,10  Praveen Kumar⁸  Santosh Renuse⁶  Anita Mahadevan⁴  Lakshmi Dhevi N Selvan⁶  S Sameer Kumar Ghantasala⁹  Abhilash K Venugopal⁹ 

[1] Department of Neurovirology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India;Bioinformatics Centre, School of Life Sciences, Pondicherry University, Pondicherry, 605014, India;Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA;Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India;Manipal University, Madhav Nagar, Manipal, Karnataka, 576104, India;Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India;Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India;Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India;Department of Biotechnology, Kuvempu University, Shimoga, 577451, India;Rajiv Gandhi University of Health Sciences, Bangalore, 560041, India

关键词: Post Exposure Vaccination;    Hierarchical cluster;    Spectrum Mill;    Mass spectrometry;    Liquid chromatography;   

Others  :  1026347
DOI  :  10.1186/1559-0275-10-3

 received in 2012-06-27, accepted in 2013-03-14,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Venugopal et al.; licensee BioMed Central Ltd.

【 图 表 】

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