Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human α2-macroglobulin and pregnancy zone protein

Ramos, Adrián M.; Duschak, Vilma G.; Burgos, Nelia M. Gerez de; Barboza, Mariana; Remedi, Marı́a S.; Vides, Miguel A.; Chiabrando, Gustavo A.

doi:10.1016/s0014-4894(02)00007-3

Cited by 22 publications

(15 citation statements)

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“…However, a 2 M Ã only recognizes LRP1 and not any other LDL receptor members [Hussain et al, 1999]. In addition, a 2 M Ã is internalized by LRP1, implying that both molecules are involved in the modulation of the extracellular activity of several proteases [Sanchez et al, 1998;Herz and Strickland, 2001;Ramos et al, 2002]. LRP1 is a cell surface glycoprotein synthesized as a 600-kDa proreceptor and post-translationally processed into 515-kDa a-subunit and 85-kDa b-subunit that remain associated through non-covalent interactions [Herz and Strickland, 2001].…”

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confidence: 99%

Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Cáceres

Bonacci

Sánchez

et al. 2010

J of Cellular Biochemistry

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Macrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-κB signaling pathways. Previously, we demonstrated that activated α(2)-macroglulin (α(2)M*) through the interaction with its receptor low-density lipoprotein receptor-related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK-ERK1/2. In the present work, we examined whether α(2)M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that α(2)M* promoted MMP-9 expression and protein secretion by LRP1 in both macrophage-derived cell lines, which was mediated by the activation of MAPK-ERK1/2 and NF-κB. Both intracellular signaling pathways activated by α(2)M* were effectively blocked by calphostin-C, suggesting involvement of PKC. In addition, we demonstrate that α(2)M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the α(2)M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1, and NF-κB, it was shown that the α(2)M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the α(2)M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.

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confidence: 99%

Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Cáceres

Bonacci

Sánchez

et al. 2010

J of Cellular Biochemistry

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“…A third protein known to inhibit cruzain is the pregnancy zone protein (PZP) [51]. PZP displays a bait region where susceptible bonds are displayed.…”

Section: Dihydrofolate Reductasementioning

confidence: 99%

Recent Developments in the Identification of Chemotherapeutics for Chagas Disease

Lockman¹,

Hamilton²

2005

CMC

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Chagas Disease, caused by the T. cruzi parasite, is one of the largest public health problems in the Western hemisphere. Although its spread has diminished due to vector eradication programs, effective chemotherapeutics for the disease itself remain elusive. Many efforts towards the development of antiparasitic agents active against a number of targets have been described recently in the literature. This review summarizes developments in trypanosidal agents from 2000 through 2003.

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“…A vaccine based on VSG would have to cover the entire repertoire of antigenic types, which is not feasible [37]. Invariant antigens that have thus far been identified as potential vaccine candidates include microtubule-associate protein p15 from T. b. brucei [5, 32] and β-tubulin from T. brucei and T. evansi [21, 23, 24]. Vaccination studies in mice have shown that these proteins may provide protection against challenge from T. b. brucei (and T. evansi and T. equiperdum for β-tubulin) [21, 23, 24, 32], but thus far, these studies have excluded homologues from T. congolense or T. vivax .…”

Section: Introductionmentioning

confidence: 99%

“…This type of vaccine may not affect the survival of the parasite, but would neutralise pathogenic factors, thereby lessening the pathological effects and possibly inducing a state of trypanotolerance [3, 32], as naturally exhibited by some African breeds of cattle [29]. It has been suggested that congopain, a cysteine protease of T. congolense, has a pathogenic role in trypanosomosis by degrading host proteins and interfering with other host processes [36].…”

Section: Introductionmentioning

confidence: 99%

Modulation of the immunogenicity of theTrypanosoma congolensecysteine protease, congopain, through complexation with α₂-macroglobulin

et al. 2009

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The protozoan parasite Trypanosoma congolense is the main causative agent of livestock trypanosomosis. Congopain, the major lysosomal cysteine proteinase of T. congolense, contributes to disease pathogenesis, and antibody-mediated inhibition of this enzyme may contribute to mechanisms of trypanotolerance. The potential of different adjuvants to facilitate the production of antibodies that would inhibit congopain activity was evaluated in the present study. Rabbits were immunised with the recombinant catalytic domain of congopain (C2), either without adjuvant, with Freund’s adjuvant or complexed with bovine or rabbit α2-macroglobulin (α2M). The antibodies were assessed for inhibition of congopain activity. Rabbits immunised with C2 alone produced barely detectable anti-C2 antibody levels and these antibodies had no effect on recombinant C2 or native congopain activity. Rabbits immunised with C2 and Freund’s adjuvant produced the highest levels of anti-C2 antibodies. These antibodies either inhibited C2 and native congopain activity to a small degree, or enhanced their activity, depending on time of production after initial immunisation. Rabbits receiving C2-α2M complexes produced moderate levels of anti-C2 antibodies and these antibodies consistently showed the best inhibition of C2 and native congopain activity of all the antibodies, with maximum inhibition of 65%. Results of this study suggest that antibodies inhibiting congopain activity could be raised in livestock with a congopain catalytic domain-α2M complex. This approach improves the effectiveness of the antigen as an anti-disease vaccine candidate for African trypanosomosis.

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Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human α2-macroglobulin and pregnancy zone protein

Cited by 22 publications

References 47 publications

Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Recent Developments in the Identification of Chemotherapeutics for Chagas Disease

Modulation of the immunogenicity of theTrypanosoma congolensecysteine protease, congopain, through complexation with α₂-macroglobulin

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Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human α2-macroglobulin and pregnancy zone protein

Cited by 22 publications

References 47 publications

Activated α2 macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Activated α2 macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Recent Developments in the Identification of Chemotherapeutics for Chagas Disease

Modulation of the immunogenicity of theTrypanosoma congolensecysteine protease, congopain, through complexation with α2-macroglobulin

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Product

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Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Activated α₂ macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines

Modulation of the immunogenicity of theTrypanosoma congolensecysteine protease, congopain, through complexation with α₂-macroglobulin