The pathological effects of Heminecrolysin, a dermonecrotic toxin from Hemiscorpius lepturus scorpion venom are mediated through its lysophospholipase D activity

Autor: Haifa Ben Gharsa, Lamia Borchani, Ines Safra, A. Sassi, Delavar Shahbazzadeh, Zakaria Ben Lasfar, Mohamed El Ayeb
Přispěvatelé: Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses (LR11IPT04), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Laboratoire d'hématologie moléculaire et cellulaire (LR11IPT07), Medical Biotechnology Group, Venom and Toxin Lab, Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Biotechnology Research Center, Réseau International des Instituts Pasteur (RIIP), The work has been financially supported by the Tunisian Ministry of Research and Technology (MERST).
Rok vydání: 2013
Předmět:
MESH: Interleukin-10
Erythrocytes
[SDV]Life Sciences [q-bio]
Chick Embryo
Phospholipase
MESH: Lysophosphatidylcholines
Toxicology
Choline
Jurkat Cells
chemistry.chemical_compound
MESH: Scorpion Venoms
Lysophosphatidic acid
MESH: Jurkat Cells
MESH: Animals
Glycophorins
0303 health sciences
MESH: Erythrocytes
030302 biochemistry & molecular biology
MESH: Choline
Spiders
MESH: Phosphatidylserines
Phosphatidylserine
MESH: Chick Embryo
MESH: Hemolysis
Interleukin-10
3. Good health
Lysophosphatidylcholine
Biochemistry
Sphingomyelin
Scorpion Venoms
MESH: Spiders
Phosphatidylserines
Biology
Hemolysis
MESH: Lysophospholipids
Scorpions
03 medical and health sciences
Classical complement pathway
MESH: Glycophorin
Phosphatidylcholine
Animals
Humans
030304 developmental biology
MESH: Humans
Interleukin-6
Phosphoric Diester Hydrolases
Tumor Necrosis Factor-alpha
Lysophosphatidylcholines
MESH: Interleukin-6
MESH: Scorpions
EGTA
chemistry
MESH: Tumor Necrosis Factor-alpha
Lysophospholipids
MESH: Phosphoric Diester Hydrolases
Zdroj: Toxicon
Toxicon, Elsevier, 2013, 68, pp.30-9. ⟨10.1016/j.toxicon.2013.03.012⟩
ISSN: 0041-0101
DOI: 10.1016/j.toxicon.2013.03.012
Popis: International audience; We have previously identified Heminecrolysin, a sphingomyelinase D (SMaseD), as the major protein responsible for the main pathological effects observed following Hemiscorpius (H.) lepturus scorpion envenomation. We aimed herein to further investigate the kinetics and molecular mechanisms triggered by Heminecrolysin to initiate hematological disorders and inflammatory reaction. We show that Heminecrolysin highly hydrolyzes lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and choline, with a Vmax = 1481 ± 51 μmol/min/mg and a Km = 97 ± 16.78 μM, at a much lesser extend sphingomyelin but not phosphatidylcholine substrates. Its lysophospholipase D (lysoPLD) catalytic efficiency, up to three orders of magnitude higher, comparatively to spider's SMaseDs (newly referred as phospholipases D; PLDs), could explain its strong hemolytic capacity. Chelating agents such as EDTA, EGTA, and 1, 10-phenantroline blocked Heminecrolysin-induced LPC hydrolysis at 98, 48, and 70% respectively. Hemolysis blockade occurs only when the toxin is added to erythrocytes in the presence of serum, source of LPC and complement, indicating that the production of LPA and the presence of complement are mandatory for hemolysis. Moreover, we show that Heminecrolysin efficiently binds to erythrocyte's membrane and provokes phosphatidylserine (PS) translocation without cleavage of glycophorin A, suggesting that, unlike spider's PLDs, complement was activated only via the classical pathway. Interestingly, Heminecrolysin was found to induce PS exposure on human nucleated Jurkat T cells, to stimulate secretion of the pro-inflammatory (TNF-α, IL-6), and anti-inflammatory (IL-10) cytokines by human monocytes, and to provoke a disseminated intravascular coagulation on chick embryo chorioallantoic membrane model system. Taken together, our results indicate that Heminecrolysin evokes the major characteristic clinical features of H. lepturus envenomation by using mainly its lysoPLD, rather than its SMaseD's, activity.
Databáze: OpenAIRE
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