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Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution.
J Proteome Res. 2015 Nov 06; 14(11):4896-906.JP

Abstract

This study demonstrates a direct role of venom protein expression alteration in the evolution of snake venom toxicity. Avian skeletal muscle contractile response to exogenously administered acetylcholine is completely inhibited upon exposure to South Australian and largely preserved following exposure to Queensland eastern brown snake Pseudonaja textilis venom, indicating potent postsynaptic neurotoxicity of the former and lack thereof of the latter venom. Label-free quantitative proteomics reveals extremely large differences in the expression of postsynaptic three-finger α-neurotoxins in these venoms, explaining the difference in the muscle contractile response and suggesting that the type of toxicity induced by venom can be modified by altered expression of venom proteins. Furthermore, the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm preparation occurs sooner upon exposure to the venom (10 μg/mL) with high expression of α-neurotoxins than the venoms containing predominately presynaptic β-neurotoxins. The study also finds that the onset of rat plasma coagulation is faster following exposure to the venoms with higher expression of venom prothrombin activator subunits. This is the first quantitative proteomic study that uses extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous tryptic peptides to directly show the differences in the expression of venom proteins.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, BIO21 Institute, University of Melbourne , 30 Flemington Road, Parkville, Victoria 3010, Australia. Monash Venom Group, Department of Pharmacology, Monash University , 9 Ancora Imparo Way, Clayton, Victoria 3800, Australia.Monash Biomedical Proteomics Facility, Monash University , 23 Innovation Walk, Clayton, Victoria 3800, Australia.Venom Supplies Pty Ltd. , Stonewell Road, Tanunda, South Australia 5352, Australia.Monash Venom Group, Department of Pharmacology, Monash University , 9 Ancora Imparo Way, Clayton, Victoria 3800, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26486890

Citation

Skejic, Jure, et al. "Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight Into Venom Toxicity Evolution." Journal of Proteome Research, vol. 14, no. 11, 2015, pp. 4896-906.
Skejic J, Steer DL, Dunstan N, et al. Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution. J Proteome Res. 2015;14(11):4896-906.
Skejic, J., Steer, D. L., Dunstan, N., & Hodgson, W. C. (2015). Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution. Journal of Proteome Research, 14(11), 4896-906. https://doi.org/10.1021/acs.jproteome.5b00764
Skejic J, et al. Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight Into Venom Toxicity Evolution. J Proteome Res. 2015 Nov 6;14(11):4896-906. PubMed PMID: 26486890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution. AU - Skejic,Jure, AU - Steer,David L, AU - Dunstan,Nathan, AU - Hodgson,Wayne C, Y1 - 2015/10/21/ PY - 2015/10/22/entrez PY - 2015/10/22/pubmed PY - 2016/9/10/medline KW - Oxyuranus scutellatus KW - Pseudonaja textilis KW - evolution KW - label-free quantification KW - neurotoxins KW - procoagulants KW - proteome KW - quantitative proteomics KW - snake venom KW - toxicity SP - 4896 EP - 906 JF - Journal of proteome research JO - J Proteome Res VL - 14 IS - 11 N2 - This study demonstrates a direct role of venom protein expression alteration in the evolution of snake venom toxicity. Avian skeletal muscle contractile response to exogenously administered acetylcholine is completely inhibited upon exposure to South Australian and largely preserved following exposure to Queensland eastern brown snake Pseudonaja textilis venom, indicating potent postsynaptic neurotoxicity of the former and lack thereof of the latter venom. Label-free quantitative proteomics reveals extremely large differences in the expression of postsynaptic three-finger α-neurotoxins in these venoms, explaining the difference in the muscle contractile response and suggesting that the type of toxicity induced by venom can be modified by altered expression of venom proteins. Furthermore, the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm preparation occurs sooner upon exposure to the venom (10 μg/mL) with high expression of α-neurotoxins than the venoms containing predominately presynaptic β-neurotoxins. The study also finds that the onset of rat plasma coagulation is faster following exposure to the venoms with higher expression of venom prothrombin activator subunits. This is the first quantitative proteomic study that uses extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous tryptic peptides to directly show the differences in the expression of venom proteins. SN - 1535-3907 UR - https://www.unboundmedicine.com/medline/citation/26486890/Label_Free__XIC__Quantification_of_Venom_Procoagulant_and_Neurotoxin_Expression_in_Related_Australian_Elapid_Snakes_Gives_Insight_into_Venom_Toxicity_Evolution_ L2 - https://doi.org/10.1021/acs.jproteome.5b00764 DB - PRIME DP - Unbound Medicine ER -