Abstract
Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease. PZP, as well as α2-macroglobulin (α2-M), are able to interact with Trypanosoma cruzi proteinases. The interaction of α2-M and PZP with cruzipain, the major cysteine proteinase of T. cruzi, was investigated. Several molecular changes on both α-M inhibitors under reaction with cruzipain were found. PAGE analysis showed: (i) formation of complexes of intermediate mobility and tetramerization of native α2-M and PZP, respectively; (ii) limited proteolysis of bait region in α2-M and PZP, and (iii) covalent binding of cruzipain to PZP and α2-M. Conformational and structural changes experimented by α-Ms correlate with modifications of the enzyme electrophoretic mobility and activity. Cruzipain-α-M complexes were also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti-cruzipain antibodies. Concomitantly, α2-M and PZP impaired the activity of cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, α-Ms were able to form covalent complexes with membrane isoforms of cysteine proteinases cross-reacting with cruzipain. The present study suggests that both human α-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 121-130 |
| Number of pages | 10 |
| Journal | Experimental Parasitology |
| Volume | 100 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Parasitology
- Immunology
Cite this
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.; Gerez De Burgos, Nelia M.; Barboza Gardner, Mariana; Remedi, María S.; Vides, Miguel A.; Chiabrando, Gustavo A.
In: Experimental Parasitology, Vol. 100, No. 2, 01.02.2002, p. 121-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Trypanosoma cruzi
T2 - Cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human α2 -macroglobulin and pregnancy zone protein
AU - Ramos, Adrián M.
AU - Duschak, Vilma G.
AU - Gerez De Burgos, Nelia M.
AU - Barboza Gardner, Mariana
AU - Remedi, María S.
AU - Vides, Miguel A.
AU - Chiabrando, Gustavo A.
PY - 2002/2/1
Y1 - 2002/2/1
N2 - Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease. PZP, as well as α2-macroglobulin (α2-M), are able to interact with Trypanosoma cruzi proteinases. The interaction of α2-M and PZP with cruzipain, the major cysteine proteinase of T. cruzi, was investigated. Several molecular changes on both α-M inhibitors under reaction with cruzipain were found. PAGE analysis showed: (i) formation of complexes of intermediate mobility and tetramerization of native α2-M and PZP, respectively; (ii) limited proteolysis of bait region in α2-M and PZP, and (iii) covalent binding of cruzipain to PZP and α2-M. Conformational and structural changes experimented by α-Ms correlate with modifications of the enzyme electrophoretic mobility and activity. Cruzipain-α-M complexes were also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti-cruzipain antibodies. Concomitantly, α2-M and PZP impaired the activity of cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, α-Ms were able to form covalent complexes with membrane isoforms of cysteine proteinases cross-reacting with cruzipain. The present study suggests that both human α-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain.
AB - Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease. PZP, as well as α2-macroglobulin (α2-M), are able to interact with Trypanosoma cruzi proteinases. The interaction of α2-M and PZP with cruzipain, the major cysteine proteinase of T. cruzi, was investigated. Several molecular changes on both α-M inhibitors under reaction with cruzipain were found. PAGE analysis showed: (i) formation of complexes of intermediate mobility and tetramerization of native α2-M and PZP, respectively; (ii) limited proteolysis of bait region in α2-M and PZP, and (iii) covalent binding of cruzipain to PZP and α2-M. Conformational and structural changes experimented by α-Ms correlate with modifications of the enzyme electrophoretic mobility and activity. Cruzipain-α-M complexes were also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti-cruzipain antibodies. Concomitantly, α2-M and PZP impaired the activity of cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, α-Ms were able to form covalent complexes with membrane isoforms of cysteine proteinases cross-reacting with cruzipain. The present study suggests that both human α-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain.
UR - http://www.scopus.com/inward/record.url?scp=0036488798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036488798&partnerID=8YFLogxK
U2 - 10.1016/S0014-4894(02)00007-3
DO - 10.1016/S0014-4894(02)00007-3
M3 - Article
C2 - 12054702
AN - SCOPUS:0036488798
VL - 100
SP - 121
EP - 130
JO - Experimental Parasitology
JF - Experimental Parasitology
SN - 0014-4894
IS - 2
ER -