From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication
Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP es...
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Veröffentlicht in: | Toxicological sciences 2017-11, Vol.160 (1), p.136-149 |
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creator | Chaubey, Kalyani Alam, Syed Imteyaz Nagar, Durga Prasad Waghmare, Chandra Kant Pant, Satish C Singh, Lokendra Srivastava, Nalini Bhattacharya, Bijoy K |
description | Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury. We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulum stress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5 h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention. |
doi_str_mv | 10.1093/toxsci/kfx162 |
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Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury. We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulum stress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5 h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfx162</identifier><identifier>PMID: 28973502</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylcholinesterase - metabolism ; Animals ; Blotting, Western ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Chemical Warfare Agents - toxicity ; Cholinesterase Inhibitors - toxicity ; Electrophoresis, Gel, Two-Dimensional ; GPI-Linked Proteins - antagonists & inhibitors ; GPI-Linked Proteins - metabolism ; Lethal Dose 50 ; Male ; Nerve Degeneration ; Nerve Tissue Proteins - metabolism ; Neurotoxicity Syndromes - etiology ; Neurotoxicity Syndromes - metabolism ; Neurotoxicity Syndromes - pathology ; Protein Interaction Maps ; Proteome ; Proteomics - methods ; Rats, Wistar ; Reproducibility of Results ; Sarin - toxicity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tandem Mass Spectrometry ; Time Factors</subject><ispartof>Toxicological sciences, 2017-11, Vol.160 (1), p.136-149</ispartof><rights>The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c306t-fdcf543350469e667c79372cba6035909d239200a334588eb49ef35e285b53a93</citedby><cites>FETCH-LOGICAL-c306t-fdcf543350469e667c79372cba6035909d239200a334588eb49ef35e285b53a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28973502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chaubey, Kalyani</creatorcontrib><creatorcontrib>Alam, Syed Imteyaz</creatorcontrib><creatorcontrib>Nagar, Durga Prasad</creatorcontrib><creatorcontrib>Waghmare, Chandra Kant</creatorcontrib><creatorcontrib>Pant, Satish C</creatorcontrib><creatorcontrib>Singh, Lokendra</creatorcontrib><creatorcontrib>Srivastava, Nalini</creatorcontrib><creatorcontrib>Bhattacharya, Bijoy K</creatorcontrib><title>From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury. We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulum stress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5 h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention.</description><subject>Acetylcholinesterase - metabolism</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Chemical Warfare Agents - toxicity</subject><subject>Cholinesterase Inhibitors - toxicity</subject><subject>Electrophoresis, Gel, Two-Dimensional</subject><subject>GPI-Linked Proteins - antagonists & inhibitors</subject><subject>GPI-Linked Proteins - metabolism</subject><subject>Lethal Dose 50</subject><subject>Male</subject><subject>Nerve Degeneration</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Neurotoxicity Syndromes - metabolism</subject><subject>Neurotoxicity Syndromes - pathology</subject><subject>Protein Interaction Maps</subject><subject>Proteome</subject><subject>Proteomics - methods</subject><subject>Rats, Wistar</subject><subject>Reproducibility of Results</subject><subject>Sarin - toxicity</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Tandem Mass Spectrometry</subject><subject>Time Factors</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFFLwzAUhYMobk4ffZX8gbrbpEkb3-Z0OhgoU8G3knY3Gl2bkUSZ_96OTp_u4ZzD5fARcp7CZQqKj6PbhtqOP802leyADDtTJqCYOtxrCQUMyEkIHwBpKkEdkwErVM4FsCF5nXnX0PiOdOq-0V_RR-8iugZ3wtg1UmfojTUGPbaRLnWk117bli7xzbo20ImJ6OmT9p03b7s1ttaxS07JkdHrgGf7OyIvs9vn6X2yeLibTyeLpOYgY2JWtREZ78ZkUqGUeZ0rnrO60hK4UKBWjCsGoDnPRFFglSk0XCArRCW4VnxEkv5v7V0IHk258bbR_qdModwRKntCZU-o61_0_c1X1eDqv_2HhP8CvDRjKQ</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Chaubey, Kalyani</creator><creator>Alam, Syed Imteyaz</creator><creator>Nagar, Durga Prasad</creator><creator>Waghmare, Chandra Kant</creator><creator>Pant, Satish C</creator><creator>Singh, Lokendra</creator><creator>Srivastava, Nalini</creator><creator>Bhattacharya, Bijoy K</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20171101</creationdate><title>From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication</title><author>Chaubey, Kalyani ; Alam, Syed Imteyaz ; Nagar, Durga Prasad ; Waghmare, Chandra Kant ; Pant, Satish C ; Singh, Lokendra ; Srivastava, Nalini ; Bhattacharya, Bijoy K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c306t-fdcf543350469e667c79372cba6035909d239200a334588eb49ef35e285b53a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetylcholinesterase - metabolism</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Chemical Warfare Agents - toxicity</topic><topic>Cholinesterase Inhibitors - toxicity</topic><topic>Electrophoresis, Gel, Two-Dimensional</topic><topic>GPI-Linked Proteins - antagonists & inhibitors</topic><topic>GPI-Linked Proteins - metabolism</topic><topic>Lethal Dose 50</topic><topic>Male</topic><topic>Nerve Degeneration</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Neurotoxicity Syndromes - metabolism</topic><topic>Neurotoxicity Syndromes - pathology</topic><topic>Protein Interaction Maps</topic><topic>Proteome</topic><topic>Proteomics - methods</topic><topic>Rats, Wistar</topic><topic>Reproducibility of Results</topic><topic>Sarin - toxicity</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Tandem Mass Spectrometry</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chaubey, Kalyani</creatorcontrib><creatorcontrib>Alam, Syed Imteyaz</creatorcontrib><creatorcontrib>Nagar, Durga Prasad</creatorcontrib><creatorcontrib>Waghmare, Chandra Kant</creatorcontrib><creatorcontrib>Pant, Satish C</creatorcontrib><creatorcontrib>Singh, Lokendra</creatorcontrib><creatorcontrib>Srivastava, Nalini</creatorcontrib><creatorcontrib>Bhattacharya, Bijoy K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chaubey, Kalyani</au><au>Alam, Syed Imteyaz</au><au>Nagar, Durga Prasad</au><au>Waghmare, Chandra Kant</au><au>Pant, Satish C</au><au>Singh, Lokendra</au><au>Srivastava, Nalini</au><au>Bhattacharya, Bijoy K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>160</volume><issue>1</issue><spage>136</spage><epage>149</epage><pages>136-149</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury. We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulum stress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5 h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention.</abstract><cop>United States</cop><pmid>28973502</pmid><doi>10.1093/toxsci/kfx162</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acetylcholinesterase - metabolism Animals Blotting, Western Brain - drug effects Brain - metabolism Brain - pathology Chemical Warfare Agents - toxicity Cholinesterase Inhibitors - toxicity Electrophoresis, Gel, Two-Dimensional GPI-Linked Proteins - antagonists & inhibitors GPI-Linked Proteins - metabolism Lethal Dose 50 Male Nerve Degeneration Nerve Tissue Proteins - metabolism Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - metabolism Neurotoxicity Syndromes - pathology Protein Interaction Maps Proteome Proteomics - methods Rats, Wistar Reproducibility of Results Sarin - toxicity Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tandem Mass Spectrometry Time Factors |
title | From the Cover: Proteome Profile of Different Rat Brain Regions After Sarin Intoxication |
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