Leishmania major metacaspase can replace yeast metacaspase in programmed cell death and has arginine-specific cysteine peptidase activity

González, Iveth J.; Desponds, Chantal; Schaff, Cédric; Mottram, Jeremy C.; Fasel, Nicolás

doi:10.1016/j.ijpara.2006.10.004

Cited by 115 publications

(156 citation statements)

References 30 publications

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“…However, their direct involvement in cell death remains controversial. Indeed, the L. major metacaspase has been able to replace the yeast metacaspase in PCD, 14 and the overexpression of L. donovani metacaspase 1 increased the sensitivity of amastigotes to PCD induced by H 2 O 2 . 17 Nevertheless, in this study, (a) metacaspase 1 has a trypsin-like and not a caspase-like activity and (b) the authors did not demonstrate that metacaspases were actually necessary for the initiation and execution of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Although metacaspase genes have been identified in the genome of all trypanosomatids, their involvement in apoptosis is still debated. [14][15][16][17] Moreover, no homologue for members of the Bcl-2 protein family has been identified in T. brucei. Finally, two genes whose transcription is upregulated late during the identification of concanavalinA-induced PCD in the procyclic form of T. brucei rhodesiense, a homologue of prohibitin and a protein called TRACK, homologous to the RACK family (receptor for activated kinase C).…”

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confidence: 99%

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Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in trypanosomatids

et al. 2008

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The link between nucleocytoplasmic transport and apoptosis remains controversial. Nucleocytoplasmic exchange of molecules seems indeed essential for the initiation and execution of the apoptotic programme; but inhibition of nuclear transport factors may also represent a powerful apoptotic trigger. The GTPase Ran (together with its partners), first discovered to be essential in nucleocytoplasmic transport, has multiple key functions in cell biology, and particularly in spindle assembly, kinetochore function and nuclear envelope assembly. Among the Ran partners studied, NTF2 appears to be solely involved in nucleocytoplasmic transport. Here, we localised Ran and several of its partners, RanBP1, CAS and NTF2, at the nuclear membrane in the trypanosomatid Leishmania major. Remarkably, these proteins fused to GFP decorated a perinuclear 'collar' of about 15 dots, colocalising at nuclear pore complexes with the homologue of nucleoporin Sec13. In the other trypanosomatid Trypanosoma brucei, RNAi knockdown of the expression of the corresponding genes resulted in an apoptosis-like phenomenon. These phenotypes show that Ran and its partners have a key function in trypanosomatids like they have in mammals. Our data, notably those about TbNTF2 RNAi, support the idea that active nucleocytoplasmic transport is not essential for the initiation and execution of apoptosis, and, rather, the impairment of this transport constitutes an intrinsic signal for triggering PCD.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in trypanosomatids

et al. 2008

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“…González et al 11 showed that L. major metacaspase has a role in cell death. These researchers showed that metacaspase gene of Leishmania major (LmjMCA) was involved in yeast cell death, similar to Saccharomyces cerevisiae metacaspase (YCA1), and that this function depends on its catalytic activity.…”

Section: Miltefosine Induces Sub-g0/g1 Phase Cell-division Arrestmentioning

confidence: 99%

“…In mammalians, caspases do not only function in PCD, but they also have functions in cell proliferation and differentiation. 11 Ambit et al 26 found that LmjMCA is expressed in actively replicating amastigotes and procyclic promastigotes, but at a lower level in metacyclic promastigotes. Over expression of LmjMCA in promastigotes leads to severe growth retardation.…”

Section: Miltefosine Induces Sub-g0/g1 Phase Cell-division Arrestmentioning

confidence: 99%

“…10 Also an arginine-directed specificity has also been shown for the Leishmania major metacaspase expressed in yeast. 11 The participation of metacaspase in PCD in yeast and plants has been studied and revealed that metacaspase play a crucial role in the induction of PCD in response to various stress agents, ageing and impairment of some biological functions. 10,[12][13][14][15] The possible role of metacaspase in the cell death pathway in protozoa lead researchers to study this attractive issue.…”

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Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum

Khademvatan¹,

Gharavi²,

Saki³

2011

Braz J Infect Dis

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Objectives: Apoptosis is the process of programmed cell death (PCD) that occurs in both animal and plant cells. Protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the PCD pathways in these organisms. Therefore we analyzed the activities of metacaspase and PARP genes in Leishmania infantum (MCAN/IR/96/LON49) treated with miltefosine. Materials and Methods: Anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. MTT assay and Annexin-V FLUOS staining by using FACS flow cytometry methods were used. Cytotoxic potential of HePC on the amastigots of L. infantum was evaluated in J774 cell line. In addition, metacaspase and PARP genes expression of treated L. infantum were studied. Results: Miltefosine led to dose-dependent death of L. infantum with features compatible with apoptosis. Over expression of metacaspase and PARP was seen 6 hr after treatment. Conclusions: Our study showed that miltefosine exerts cytotoxic effect on L. infantum via an apoptotic-related mechanism.

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Peptidases in Autophagy are Therapeutic Targets for Leishmaniasis

Williams¹

2013

Trypanosomatid Diseases

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Leishmania major metacaspase can replace yeast metacaspase in programmed cell death and has arginine-specific cysteine peptidase activity

Cited by 115 publications

References 30 publications

Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in trypanosomatids

Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in trypanosomatids

Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum

Peptidases in Autophagy are Therapeutic Targets for Leishmaniasis

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