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Venoms and Toxins


ISSN (Print): 2666-1217
ISSN (Online): 2666-1225

Research Article

Top-down and Bottom-up Approaches Revealed New Categories of Peptides from the Venom of Moroccan Scorpion Androctonus mauretanicus

Author(s): Khadija Daoudi, Christian Malosse, Bouchra Darkaoui, Salma Chakir, Fatima Chgoury, Rachida Cadi, Jean-Marc Sabatier, Julia Chamot-Rooke and Naoual Oukkache*

Volume 2, Issue 1, 2022

Published on: 01 April, 2021

Article ID: e010421192615 Pages: 16

DOI: 10.2174/2666121701666210401120929


Background: Androctonus mauretanicus (Am ) is one of the most hazardous scorpions in Morocco and has a highly toxic venom responsible for severe cases of envenomation. However, few studies have focused on deciphering its proteic composition.

Objectives: Herein, we aim to map out the complete proteome of the Am venom filtrate to highlight its complexity and the polymorphism of its toxic content. This, in turn, will lead to a deeper understanding of the toxins’ mechanism of action and will help uncover those with therapeutic potential.

Methods: Top-down and bottom-up proteomic approaches were used complementarily to decipher the proteome of the Am venom. These approaches were carried out on nano-high liquid chromatography coupled to nano-electrospray tandem mass spectrometry (Nano-LC-ESI-MS/MS).

Results: Am venom encloses a complex mixture of 269 different compounds with molecular weights ranging from 1618.74 to 14 214.84 Da. The most abundant ones showed masses from 6185.92 to 7899.53 Da (53.89%) followed by those ranging from 2079.25 to 5969.63 Da (37.81%). Interestingly, the combination of the results of both approaches allowed the screening of a total of 112 peptides. The highest percentage was represented by neuropeptides (87%), including NaTxs, KTxs, ClTxs, venom proteins, venom neuropeptides, and myotropic neuropeptides. Moreover, other peptides were identified, such as antimicrobial peptides, amphipathic peptides, cysteine-rich venom peptides, enzymes, kunitz-type inhibitors and orphan peptides.

Conclusion: The Am venom appears to contain a great number of diverse peptides, some of which could prospectively be exploited for their pharmaceutical potential.

Keywords: Scorpion venom, Androctonus mauretanicus scorpion, toxins, top-down, bottom-up, venomic.

Chippaux JP, Goyffon M. Epidemiology of scorpionism: a global appraisal. Acta Trop 2008; 107(2): 71-9.
[] [PMID: 18579104]
Touloun O, Boumezzough A, Slimani T. Scorpion envenomation in the region of Marrakesh Tensift Alhaouz (Morocco): epidemiological characterization and therapeutic approaches. Serket 2012; 13: 38-50.
[3 ]
Soulaymani R, Semlali I, Skali S, Tebaa A. Episémilogie des piqures de scorpions au Maroc. Espérence médicale 1999; 51
Soulaymani R, Soulaymani A, Semlali I, et al. Les piqures et les envenimations scorpioniques au niveau de la population de Khouribga (Maroc). Bull Soc Pathol Exot 2005; 98(5): 36-40.
Ghalim N, Goudey-Perrière F, Benoit E, Goyffon M, Marchot P. Données épidémiologiques sur l’envenimation scorpionique au Maroc Collection Rencontres en toxicologie. Librairie Lavoisier 2006; pp. 295-300.
Ghazal A, Ismail M, Abdel-Rahman AA, El-Asmar MF. Pharmacological studies of scorpion (Androctonus amoreuxi Aud. & Sav.) venom. Toxicon 1975; 13(4): 253-9.
[] [PMID: 1166465]
Cupo P, Jurca M, Azeedo-Marques MM, Oliveira JSM, Hering SE. Severe scorpion envenomation in Brazil. Clinical, laboratory and anatomopathological aspects. Rev Inst Med Trop São Paulo 1994; 36(1): 67-76.
[] [PMID: 7997776]
Petricevich VL. Scorpion venom and the inflammatory response. Mediators Inflamm 2010; 2010: 903295-10.
[] [PMID: 20300540]
Cupo P. Clinical update on scorpion envenoming. Rev Soc Bras Med Trop 2015; 48(6): 642-9.
[] [PMID: 26676487]
Konca C, Tekin M, Genc Y, Turgut M. Epidemiological and clinical characteristics and outcomes of scorpion envenomation in hospitalized children in adiyaman, Turkey. Iran J Pediatr 2015; 25(1): e199.
[] [PMID: 26199687]
Cologna CT, Marcussi S, Giglio JR, Soares AM, Arantes EC. Tityus serrulatus scorpion venom and toxins: an overview. Protein Pept Lett 2009; 16(8): 920-32.
[] [PMID: 19689419]
Çağlar A, Köse H, Babayiğit A, Öner T, Duman M. Predictive factors for determining the clinical severity of pediatric scorpion envenomation cases in Southeastern Turkey. Wilderness Environ Med 2015; 26(4): 451-8.
[] [PMID: 26432426]
Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion toxins specific for Na+-channels. Eur J Biochem 1999; 264(2): 287-300.
[] [PMID: 10491073]
Rodríguez de la Vega RC, Possani LD. Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 2005; 46(8): 831-44.
[] [PMID: 16274721]
Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T. Voltage-gated ion channels and gating modifier toxins. Toxicon 2007; 49(2): 124-41.
[] [PMID: 17239913]
Quintero-Hernández V, Jiménez-Vargas JM, Gurrola GB, Valdivia HH, Possani LD. Scorpion venom components that affect ion-channels function. Toxicon 2013; 76(76): 328-42.
[] [PMID: 23891887]
Sunagar K, Undheim EA, Chan AH, et al. Evolution stings: the origin and diversification of scorpion toxin peptide scaffolds. Toxins (Basel) 2013; 5(12): 2456-87.
[] [PMID: 24351712]
Harrison PL, Abdel-Rahman MA, Miller K, Strong PN. Antimicrobial peptides from scorpion venoms. Toxicon 2014; 88: 115-37.
[] [PMID: 24951876]
Ghalim N, El-Hafny B, Sebti F, et al. Scorpion envenomation and serotherapy in Morocco. Am J Trop Med Hyg 2000; 62(2): 277-83.
[] [PMID: 10813485]
Oukkache N, El Jaoudi R, Ghalim N, et al. Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes. Toxins 2014; 6(6): 1873-81.
[] [PMID: 24926799]
[21 ]
Daoudi K, Chgoury F, Rezzak M. Consequences of Androctonus mauretanicus and Buthus occitanus scorpion venoms on electrolyte levels in rabbits. Heliyon 2017; 3(1)
Rosso JP, Rochat H. Characterization of ten proteins from the venom of the Moroccan scorpion Androctonus mauretanicus mauretanicus, six of which are toxic to the mouse. Toxicon 1985; 23(1): 113-25.
[] [PMID: 3992595]
Zerrouk H, Bougis PE, Céard B, Benslimane A, Martin-Eauclaire MF. Analysis by high-performance liquid chromatography of Androctonus mauretanicus mauretanicus (black scorpion) venom. Toxicon 1991; 29(8): 951-60.
[] [PMID: 1949066]
Zerrouk H, Mansuelle P, Benslimane A, Rochat H, Martin-Eauclaire MF. Characterization of a new leiurotoxin I-like scorpion toxin. PO5 from Androctonus mauretanicus . FEBS Lett 1993; 320(3): 189-92.
[] [PMID: 8385026]
Zerrouk H, Laraba-Djebari F, Fremont V, et al. Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+ activated K+ channel. Int J Pept Protein Res 1996; 48(6): 514-21.
[] [PMID: 8985784]
Vacher H, Alami M, Crest M, Possani LD, Bougis PE, Martin-Eauclaire MF. Expanding the scorpion toxin alpha-KTX 15 family with AmmTX3 from Androctonus mauretanicus . Eur J Biochem 2002; 269(24): 6037-41.
[] [PMID: 12473099]
Oukkache N, Rosso JP, Alami M, et al. New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom. Toxicon 2008; 51(5): 835-52.
[] [PMID: 18243273]
Martin-Eauclaire MF, Granjeaud S, Belghazi M, Bougis PE. Achieving automated scorpion venom mass fingerprinting (VMF) in the nanogram range. Toxicon 2013; 69: 211-8.
[] [PMID: 23500507]
Reid GE, McLuckey SA. ‘Top down’ protein characterization via tandem mass spectrometry. J Mass Spectrom 2002; 37(7): 663-75.
[] [PMID: 12124999]
Nesvizhskii AI, Aebersold R. Interpretation of shotgun proteomic data: the protein inference problem. Mol Cell Proteomics 2005; 4(10): 1419-40.
[] [PMID: 16009968]
Compton PD, Kelleher NL. Spinning up mass spectrometry for whole protein complexes. Nat Methods 2012; 9(11): 1065-6.
[] [PMID: 23132117]
Smith LM, Kelleher NL. Proteoform: a single term describing protein complexity. Nat Methods 2013; 10(3): 186-7.
[] [PMID: 23443629]
Melani RD, Goto-Silva L, Nogueira FCS, et al. Shotgun approaches for venom analysis.Venom genomics proteomics. Netherlands: Springer 2014; pp. 1-12.
Melani RD, Skinner OS, Fornelli L, Domont GB, Compton PD, Kelleher NL. Mapping proteoforms and protein complexes from king cobra venom using both denaturing and native top-down proteomics. Mol Cell Proteomics 2016; 15(7): 2423-34.
[] [PMID: 27178327]
Mayne J, Ning Z, Zhang X, et al. Bottom-up proteomics (2013–2015): keeping up in the era of systems biology. Anal Chem 2016; 88(1): 95-121.
[] [PMID: 26558748]
Fornelli L, Toby TK, Schachner LF, et al. Top-down proteomics: Where we are, where we are going? J Proteomics 2018; 175: 3-4.
[] [PMID: 28188863]
Melani RD, Nogueira FCS, Domont GB. It is time for top-down venomics. J Venom Anim Toxins Incl Trop Dis 2017; 23: 44.
[] [PMID: 29075288]
Oukkache N, Chgoury F, Lalaoui M, Cano AA, Ghalim N. Comparison between two methods of scorpion venom milking in Morocco. J Venom Anim Toxins Incl Trop Dis 2013; 19(1): 5.
[] [PMID: 23849043]
DeBin JA, Maggio JE, Strichartz GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol 1993; 264(2 Pt 1): C361-9.
[] [PMID: 8383429]
Gu Y, Liu SL, Ju WZ, Li CY, Cao P. Analgesic-antitumor peptide induces apoptosis and inhibits the proliferation of SW480 human colon cancer cells. Oncol Lett 2013; 5(2): 483-8.
[] [PMID: 23420047]
Possani LD, Alagón AC, Fletcher PL Jr, Erickson BW. Purification and properties of mammalian toxins from the venom of Brazilian Scorpion Tityus serrulatus Lutz and Mello. Arch Biochem Biophys 1977; 180(2): 394-403.
[] [PMID: 879793]
Pessini AC, Takao TT, Cavalheiro EC, et al. A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids. Toxicon 2001; 39(10): 1495-504.
[] [PMID: 11478957]
Cid-Uribe JI, Meneses EP, Batista CVF, Ortiz E, Possani LD. Dissecting toxicity: The venom gland transcriptome and the venom proteome of the highly venomous scorpion Centruroides limpidus (Karsch, 1879). Toxins 2019; 11(5): 247.
[] [PMID: 31052267]
Pascual N, Castresana J, Valero ML, Andreu D, Bellés X. Orcokinins in insects and other invertebrates. Insect Biochem Mol Biol 2004; 34(11): 1141-6.
[] [PMID: 15522610]
Hofer S, Dircksen H, Tollbäck P, Homberg U. Novel insect orcokinins: characterization and neuronal distribution in the brains of selected dicondylian insects. J Comp Neurol 2005; 490(1): 57-71.
[] [PMID: 16041719]
Conde R, Zamudio FZ, Rodríguez MH, Possani LD. Scorpine, an anti-malaria and anti-bacterial agent purified from scorpion venom. FEBS Lett 2000; 471(2-3): 165-8.
[] [PMID: 10767415]
Ehret-Sabatier L, Loew D, Goyffon M, et al. Characterization of novel cysteine-rich antimicrobial peptides from scorpion blood. J Biol Chem 1996; 271(47): 29537-44.
[] [PMID: 8939880]
Almaaytah A, Tarazi S, Mhaidat N, Al-Balas Q, Mukattash TL. Mauriporin, a novel cationic α-helical peptide with selective cytotoxic activity against prostate cancer cell lines from the venom of the scorpion Androctonus mauritanicus. Int J Pept Res Ther 2013; 19(4): 281-93.
Grashof DGB, Kerkkamp HMI, Afonso S, et al. Transcriptome annotation and characterization of novel toxins in six scorpion species. BMC Genomics 2019; 20(1): 645.
[] [PMID: 31409288]
Verano-Braga T, Rocha-Resende C, Silva DM, et al. Tityus serrulatus Hypotensins: a new family of peptides from scorpion venom. Biochem Biophys Res Commun 2008; 371(3): 515-20.
[] [PMID: 18445483]
Rates B, Ferraz KK, Borges MH, Richardson M, De Lima ME, Pimenta AM. Tityus serrulatus venom peptidomics: assessing venom peptide diversity. Toxicon 2008; 52(5): 611-8.
[] [PMID: 18718845]
Alves RS, Ximenes RM, Jorge AR, et al. Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus ). Toxicon 2013; 74: 19-26.
[] [PMID: 23911732]
Horta CC, Magalhães BdeF, Oliveira-Mendes BB, et al. Molecular, immunological, and biological characterization of Tityus serrulatus venom hyaluronidase: new insights into its role in envenomation. PLoS Negl Trop Dis 2014; 8(2): e2693.
[] [PMID: 24551256]
Carmo AO, Oliveira-Mendes BB, Horta CC, et al. Molecular and functional characterization of metalloserrulases, new metalloproteases from the Tityus serrulatus venom gland. Toxicon 2014; 90: 45-55.
[] [PMID: 25091350]
Pucca MB, Cerni FA, Pinheiro-Junior EL, et al. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors. Peptides 2016; 82: 44-51.
[] [PMID: 27221550]
Duzzi B, Cajado-Carvalho D, Kuniyoshi AK, et al. [des-Arg(1)]-Proctolin: A novel NEP-like enzyme inhibitor identified in Tityus serrulatus venom. Peptides 2016; 80: 18-24.
[] [PMID: 26056922]
Cajado-Carvalho D, Kuniyoshi AK, Duzzi B, et al. Insights into the hypertensive effects of Tityus serrulatus scorpion venom: Purification of an angiotensin-converting enzyme-like peptidase. Toxins 2016; 8(12): E348.
[] [PMID: 27886129]
de Oliveira UC, Nishiyama MY Jr, Dos Santos MBV, et al. Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions. PLoS One 2018; 13(3): e0193739.
[] [PMID: 29561852]
Romero-Gutiérrez MT, Santibáñez-López CE, Jiménez-Vargas JM, Batista CVF, Ortiz E, Possani LD. Transcriptomic and proteomic analyses reveal the diversity of venom components from the vaejovid scorpion Serradigitus gertschi. Toxins (Basel) 2018; 10(9): E359.
[] [PMID: 30189638]
Verano-Braga T, Dutra AA, León IR, et al. Moving pieces in a venomic puzzle: unveiling post-translationally modified toxins from Tityus serrulatus. J Proteome Res 2013; 12(7): 3460-70.
[] [PMID: 23731212]
Caliskan F, Quintero-Hernández V, Restano-Cassulini R, et al. Turkish scorpion Buthacus macrocentrus: general characterization of the venom and description of Bu1, a potent mammalian Na+-channel α-toxin. Toxicon 2012; 59(3): 408-15.
[] [PMID: 22245624]
Carcamo-Noriega EN, Olamendi-Portugal T, Restano-Cassulini R, et al. Intraspecific variation of Centruroides sculpturatus scorpion venom from two regions of Arizona. Arch Biochem Biophys 2018; 638: 52-7.
[] [PMID: 29258861]
D’Suze G, Sandoval M, Sevcik C. Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species. Toxicon 2015; 108: 62-72.
[] [PMID: 26415902]
Kuzmenkov AI, Vassilevski AA, Kudryashova KS, et al. Variability of potassium channel blockers in Mesobuthus eupeus scorpion venom with focus on Kv1.1: an integrated transcriptomic and proteomic study. J Biol Chem 2015; 290(19): 12195-209.
[] [PMID: 25792741]
Abdel-Rahman MA, Omran MA, Abdel-Nabi IM, Ueda H, McVean A. Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes. Toxicon 2009; 53(3): 349-59.
[] [PMID: 19103215]
Aboumaâd B, Iba N, Dersi N. Scorpion envenomation in Morocco: scorpions of the genus Androctonus, Buthus and Hottentota. Bull Soc Pathol Exot 2014; 107(1): 39-47.
[] [PMID: 24402964]

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