2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia

Ashish Kumar Gupta,1 Gaurav Khunger Kumar,1 Komal Rani,1 Ruchika Pokhriyal,1 Mohd Imran Khan,1 Domada Ratna Kumar,1 Vinay Goyal,2 Manjari Tripathi,2 Rishab Gupta,3 Rakesh Kumar Chadda,3 Perumal Vanamail,4 Ashok Kumar Mohanty,5 Gururao Hariprasad1 1Department of Biophysics, All India Institute of Me...

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Autores principales:	Gupta AK, Kumar GK, Rani K, Pokhriyal R, Khan MI, Kumar DR, Goyal V, Tripathi M, Gupta R, Chadda RK, Vanamail P, Mohanty AK, Hariprasad G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Parkinson’s disease Schizophrenia Gel based proteomics biomarkers dopamine pharmacological efficacy Difference Gel Electrophoresis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d1f03446655b4c2bbb0e1c8fd3de207d
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spelling	oai:doaj.org-article:d1f03446655b4c2bbb0e1c8fd3de207d2021-12-02T06:01:58Z2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia1178-2021https://doaj.org/article/d1f03446655b4c2bbb0e1c8fd3de207d2019-04-01T00:00:00Zhttps://www.dovepress.com/2d-dige-as-a-strategy-to-identify-serum-protein-biomarkers-to-monitor--peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Ashish Kumar Gupta,1 Gaurav Khunger Kumar,1 Komal Rani,1 Ruchika Pokhriyal,1 Mohd Imran Khan,1 Domada Ratna Kumar,1 Vinay Goyal,2 Manjari Tripathi,2 Rishab Gupta,3 Rakesh Kumar Chadda,3 Perumal Vanamail,4 Ashok Kumar Mohanty,5 Gururao Hariprasad1 1Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India; 2Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India; 3Department of Psychiatry, All India Institute of Medical Sciences, New Delhi 110029, India; 4Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India; 5Proteomics Facility, National Diary Research Institute, Karnal, Haryana 132001, India Objectives: Parkinson’s disease and schizophrenia are clinical scenarios that occur due to dopaminergic deficit and hyperactivity in the midbrain, respectively. Current pharmacological interventions for these two diseases therefore aim to restore normal dopamine levels in the midbrain. But during therapy, there is a overshooting of dopamine concentrations that result in hallucinations in Parkinson’s disease patients and extra-pyramidal symptoms in schizophrenic patients. This causes a lot of inconvenience to the patents and the clinicians. There are no tests currently available to monitor drug efficacy in these two neuropsychiatric diseases. Materials and methods: Parkinson’s disease and schizophrenic naïve patients were recruited. Serum proteins isolated from these two clinical phenotypes were labeled with fluorescent cyanine dyes and analyzed by two-dimensional difference in gel electrophoresis proteomic experiment. Differentially expressed spots that had consistent expression pattern across five sets of biological replicate gels were trypsin digested and subjected to mass spectrometric analysis for protein identification. Validation experiments were done for the identified proteins using antibody-based assay on a patient cohort that included naïve, treated, and those who had side effects. Results: Serum α- and β-globin chains were identified as differentially expressed proteins having threefold higher expressions in Parkinson’s patients as compared to schizophrenia. Interestingly, concentrations of these two proteins had an inverse correlation across clinical phenotypes in the dopaminergic spectrum. RBC contamination as a source for these proteins was ruled out. Conclusion: There is a clear association of free serum globin with dopaminergic clinical states. This lays a platform for protein biomarker–based monitoring of pharmacological efficacy in Parkinson’s disease and schizophrenia. Keywords: Parkinson’s disease, schizophrenia, gel-based proteomics, biomarkers, dopamine, pharmacological efficacy, difference gel electrophoresisGupta AKKumar GKRani KPokhriyal RKhan MIKumar DRGoyal VTripathi MGupta RChadda RKVanamail PMohanty AKHariprasad GDove Medical PressarticleParkinson’s diseaseSchizophreniaGel based proteomicsbiomarkersdopaminepharmacological efficacyDifference Gel ElectrophoresisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 1031-1044 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease Schizophrenia Gel based proteomics biomarkers dopamine pharmacological efficacy Difference Gel Electrophoresis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Parkinson’s disease Schizophrenia Gel based proteomics biomarkers dopamine pharmacological efficacy Difference Gel Electrophoresis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Gupta AK Kumar GK Rani K Pokhriyal R Khan MI Kumar DR Goyal V Tripathi M Gupta R Chadda RK Vanamail P Mohanty AK Hariprasad G 2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
description	Ashish Kumar Gupta,1 Gaurav Khunger Kumar,1 Komal Rani,1 Ruchika Pokhriyal,1 Mohd Imran Khan,1 Domada Ratna Kumar,1 Vinay Goyal,2 Manjari Tripathi,2 Rishab Gupta,3 Rakesh Kumar Chadda,3 Perumal Vanamail,4 Ashok Kumar Mohanty,5 Gururao Hariprasad1 1Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India; 2Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India; 3Department of Psychiatry, All India Institute of Medical Sciences, New Delhi 110029, India; 4Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India; 5Proteomics Facility, National Diary Research Institute, Karnal, Haryana 132001, India Objectives: Parkinson’s disease and schizophrenia are clinical scenarios that occur due to dopaminergic deficit and hyperactivity in the midbrain, respectively. Current pharmacological interventions for these two diseases therefore aim to restore normal dopamine levels in the midbrain. But during therapy, there is a overshooting of dopamine concentrations that result in hallucinations in Parkinson’s disease patients and extra-pyramidal symptoms in schizophrenic patients. This causes a lot of inconvenience to the patents and the clinicians. There are no tests currently available to monitor drug efficacy in these two neuropsychiatric diseases. Materials and methods: Parkinson’s disease and schizophrenic naïve patients were recruited. Serum proteins isolated from these two clinical phenotypes were labeled with fluorescent cyanine dyes and analyzed by two-dimensional difference in gel electrophoresis proteomic experiment. Differentially expressed spots that had consistent expression pattern across five sets of biological replicate gels were trypsin digested and subjected to mass spectrometric analysis for protein identification. Validation experiments were done for the identified proteins using antibody-based assay on a patient cohort that included naïve, treated, and those who had side effects. Results: Serum α- and β-globin chains were identified as differentially expressed proteins having threefold higher expressions in Parkinson’s patients as compared to schizophrenia. Interestingly, concentrations of these two proteins had an inverse correlation across clinical phenotypes in the dopaminergic spectrum. RBC contamination as a source for these proteins was ruled out. Conclusion: There is a clear association of free serum globin with dopaminergic clinical states. This lays a platform for protein biomarker–based monitoring of pharmacological efficacy in Parkinson’s disease and schizophrenia. Keywords: Parkinson’s disease, schizophrenia, gel-based proteomics, biomarkers, dopamine, pharmacological efficacy, difference gel electrophoresis
format	article
author	Gupta AK Kumar GK Rani K Pokhriyal R Khan MI Kumar DR Goyal V Tripathi M Gupta R Chadda RK Vanamail P Mohanty AK Hariprasad G
author_facet	Gupta AK Kumar GK Rani K Pokhriyal R Khan MI Kumar DR Goyal V Tripathi M Gupta R Chadda RK Vanamail P Mohanty AK Hariprasad G
author_sort	Gupta AK
title	2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
title_short	2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
title_full	2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
title_fullStr	2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
title_full_unstemmed	2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia
title_sort	2d-dige as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of parkinson’s disease and schizophrenia
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d1f03446655b4c2bbb0e1c8fd3de207d
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2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson&rsquo;s disease and schizophrenia

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2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia