Titre
Cathepsin B-like and cell death in the unicellular human pathogen Leishmania.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
El-Fadili, A.K.
Auteure/Auteur
Zangger, H.
Auteure/Auteur
Desponds, C.
Auteure/Auteur
Gonzalez, I.J.
Auteure/Auteur
Zalila, H.
Auteure/Auteur
Schaff, C.
Auteure/Auteur
Ives, A.
Auteure/Auteur
Masina, S.
Auteure/Auteur
Mottram, J.C.
Auteure/Auteur
Fasel, N.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2041-4889
Statut éditorial
Publié
Date de publication
2010
Volume
1
Numéro
9
Première page
e71
Langue
anglais
Résumé
In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H(2)O(2)), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes.
PID Serval
serval:BIB_1CDC93F3BF21
PMID
Open Access
Oui
Date de création
2010-11-26T09:19:48.811Z
Date de création dans IRIS
2025-05-20T17:47:02Z
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Nom
BIB_1CDC93F3BF21.P001.pdf
Version du manuscrit
preprint
Taille
592.59 KB
Format
Adobe PDF
PID Serval
serval:BIB_1CDC93F3BF21.P001
URN
urn:nbn:ch:serval-BIB_1CDC93F3BF212
Somme de contrôle
(MD5):604a704926965f3462a5853e95aab9df