Increased expression of immune modulator proteins and decreased expression of apolipoprotein A-1 and haptoglobin in blood plasma of sarin exposed rats
| Autor: | S. Imteyaz Alam, B.K. Bhattacharya, M. Kameshwar Rao, Kalyani Chaubey, Chandrakant Waghmare |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Proteomics 0301 basic medicine medicine.medical_specialty Sarin Synaptic cleft Toxicology Immunomodulation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Muscarinic acetylcholine receptor medicine Animals Rats Wistar Psychomotor function Apolipoprotein A-I Haptoglobins Chemistry Neurotoxicity General Medicine medicine.disease Blood proteins Acetylcholinesterase Rats 030104 developmental biology Endocrinology Gene Expression Regulation Biomarkers 030217 neurology & neurosurgery Acetylcholine medicine.drug |
| Zdroj: | Chemico-Biological Interactions. 246:36-44 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2016.01.008 |
| Popis: | Sarin is a highly toxic organophosphonate and neural enzyme acetylcholinesterase (AChE) inhibitor. Inhibition of AChE causes large accumulation of acetylcholine at synaptic cleft leading to hyper activation of nicotinic and muscarinic acetylcholine receptors, causing excessive secretions, muscle fasciculation, nausea, vomiting, respiratory distress and neurological effects. There are cases in which long term psychomotor function deficiency, reduced learning and memory functions have been observed several years after exposure of sarin among survivors. This phenomenon is called Organophosphorus ester Induced Chronic Neurotoxicity (OPICN) and cannot be explained by AChE inhibition alone. Plasma proteomics at earlier stages was carried out to study changes reflected at blood level that can help predict possible neurological insults at an early time point to take proper therapeutic interventions against OPICN. In the present study, a 0.5 LD50 dose of sarin was administered to Wistar rats and possible changes in blood plasma proteomic profile were investigated after one and seven days of sarin exposure. Proteins were separated on 2-dimensional gel electrophoresis and identified by MALDI-TOF/MS. Expression profile of major proteins was validated by Western blot. Result showed that after exposure of sarin inhibition of AChE persisted after one week of exposure. There were 14 plasma proteins that showed significant changes in expression (>1.5-fold). It included proteins related to immune function, neurodegenerative condition and chaperone function. Interestingly sarin exposure caused decreased expression of plasma Apolipoprotein A-1 and Haptoglobin on day seven, which are the putative early molecular markers for cognitive impairment and neurodegenerative changes. |
| Databáze: | OpenAIRE |
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