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Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation
Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in Leishmania...
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| Published in: | Experimental parasitology 2006-10, Vol.114 (2), p.94-102 |
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| creator | Brobey, Reynolds K.B. Soong, Lynn |
| description | Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether
Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in
Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In
L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37–55
°C) than that in promastigote lysates.
Leishmania TGase differs from mouse macrophage (MΦ) TGase in two ways: (1) the parasite enzyme is Ca
2+-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for
L. amazonensis TGase were found within the 50–75
kDa region, while those for the MΦ TGase were located within 37–50
kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for
L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival. |
| doi_str_mv | 10.1016/j.exppara.2006.02.021 |
| format | article |
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Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in
Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In
L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37–55
°C) than that in promastigote lysates.
Leishmania TGase differs from mouse macrophage (MΦ) TGase in two ways: (1) the parasite enzyme is Ca
2+-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for
L. amazonensis TGase were found within the 50–75
kDa region, while those for the MΦ TGase were located within 37–50
kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for
L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2006.02.021</identifier><identifier>PMID: 16620812</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject><![CDATA[2-[ N-morpholino]ethanesulfonic acid ; Amastigote ; Animals ; BCA ; bicinchonic acid ; Biological and medical sciences ; Blotting, Western ; Cadaverine - analogs & derivatives ; Cadaverine - pharmacology ; Cells, Cultured ; Colorimetry ; cystamine ; Cystamine - pharmacology ; DDC ; didansylcadaverine ; Enzyme Inhibitors - pharmacology ; fluorescein cadaverine ; Fundamental and applied biological sciences. Psychology ; Glycoconjugates ; Hydrogen-Ion Concentration ; Inhibition ; IodoA ; iodoacetamide ; Iodoacetamide - pharmacology ; Leishmania ; Leishmania - drug effects ; Leishmania - enzymology ; Leishmania - growth & development ; Leishmania infantum - drug effects ; Leishmania infantum - enzymology ; Leishmania infantum - growth & development ; Leishmania major - drug effects ; Leishmania major - enzymology ; Leishmania major - growth & development ; Leishmania mexicana - drug effects ; Leishmania mexicana - enzymology ; Leishmania mexicana - growth & development ; Life cycle. Host-agent relationship. Pathogenesis ; macrophage ; Macrophages - enzymology ; MDC ; MES ; Mice ; Mice, Inbred BALB C ; monodansylcadaverine ; Parasite ; posttranslational modification ; Promastigote ; Protozoa ; PTM ; Temperature ; TGase ; transglutaminase ; Transglutaminase (EC 2.3.2.13) ; Transglutaminases - analysis ; Transglutaminases - antagonists & inhibitors ; Transglutaminases - physiology ; Trypanosomatid ; Western blot]]></subject><ispartof>Experimental parasitology, 2006-10, Vol.114 (2), p.94-102</ispartof><rights>2006 Elsevier Inc.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-f9a4a9bcb59eadcfa6d3bdf6f209948c7fa6bd56adc9135613ef99b58f0c73d03</citedby><cites>FETCH-LOGICAL-c424t-f9a4a9bcb59eadcfa6d3bdf6f209948c7fa6bd56adc9135613ef99b58f0c73d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18194428$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16620812$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brobey, Reynolds K.B.</creatorcontrib><creatorcontrib>Soong, Lynn</creatorcontrib><title>Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether
Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in
Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In
L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37–55
°C) than that in promastigote lysates.
Leishmania TGase differs from mouse macrophage (MΦ) TGase in two ways: (1) the parasite enzyme is Ca
2+-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for
L. amazonensis TGase were found within the 50–75
kDa region, while those for the MΦ TGase were located within 37–50
kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for
L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival.</description><subject>2-[ N-morpholino]ethanesulfonic acid</subject><subject>Amastigote</subject><subject>Animals</subject><subject>BCA</subject><subject>bicinchonic acid</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cadaverine - analogs & derivatives</subject><subject>Cadaverine - pharmacology</subject><subject>Cells, Cultured</subject><subject>Colorimetry</subject><subject>cystamine</subject><subject>Cystamine - pharmacology</subject><subject>DDC</subject><subject>didansylcadaverine</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>fluorescein cadaverine</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycoconjugates</subject><subject>Hydrogen-Ion Concentration</subject><subject>Inhibition</subject><subject>IodoA</subject><subject>iodoacetamide</subject><subject>Iodoacetamide - pharmacology</subject><subject>Leishmania</subject><subject>Leishmania - drug effects</subject><subject>Leishmania - enzymology</subject><subject>Leishmania - growth & development</subject><subject>Leishmania infantum - drug effects</subject><subject>Leishmania infantum - enzymology</subject><subject>Leishmania infantum - growth & development</subject><subject>Leishmania major - drug effects</subject><subject>Leishmania major - enzymology</subject><subject>Leishmania major - growth & development</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - enzymology</subject><subject>Leishmania mexicana - growth & development</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>macrophage</subject><subject>Macrophages - enzymology</subject><subject>MDC</subject><subject>MES</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>monodansylcadaverine</subject><subject>Parasite</subject><subject>posttranslational modification</subject><subject>Promastigote</subject><subject>Protozoa</subject><subject>PTM</subject><subject>Temperature</subject><subject>TGase</subject><subject>transglutaminase</subject><subject>Transglutaminase (EC 2.3.2.13)</subject><subject>Transglutaminases - analysis</subject><subject>Transglutaminases - antagonists & inhibitors</subject><subject>Transglutaminases - physiology</subject><subject>Trypanosomatid</subject><subject>Western blot</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkV9rHCEUxSW0JNs0H6HFl_Zttuo47tiXEkKaFBb60j7LHb2mLvOv6i7Nt6_DDuQxcEG5_q73cA4hHzjbcsbVl8MW_80zRNgKxtSWiVL8gmw406wSUuo3ZMMYl5Vstbwi71I6MMZaLuQlueJKieW-IbDHkP4MMAagaUYbMH2l96fgcLRI_RRpjjCmp_6YYQgjJKRgcziF_ExhdDTkROPUIw0jXdSkkJHOpRM8RshhGt-Ttx76hDfreU1-f7__dfdY7X8-_Li73VdWCpkrr0GC7mzXaARnPShXd84rL5jWsrW70ulco8qb5nWjeI1e665pPbO72rH6mnw-_1u2_z1iymYIyWLfw4jTMRnVtkpx3b4Kcl23nO3qAjZn0MYppYjezDEMEJ8NZ2YJwRzMGoJZQjBMlOJl7uO64NgN6F6mVtcL8GkFIFnofXHYhvTCtVxLKRal384cFt9OAaNJJaASjAsRbTZuCq9I-Q8hpKqL</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Brobey, Reynolds K.B.</creator><creator>Soong, Lynn</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>20061001</creationdate><title>Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation</title><author>Brobey, Reynolds K.B. ; Soong, Lynn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-f9a4a9bcb59eadcfa6d3bdf6f209948c7fa6bd56adc9135613ef99b58f0c73d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>2-[ N-morpholino]ethanesulfonic acid</topic><topic>Amastigote</topic><topic>Animals</topic><topic>BCA</topic><topic>bicinchonic acid</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cadaverine - analogs & derivatives</topic><topic>Cadaverine - pharmacology</topic><topic>Cells, Cultured</topic><topic>Colorimetry</topic><topic>cystamine</topic><topic>Cystamine - pharmacology</topic><topic>DDC</topic><topic>didansylcadaverine</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>fluorescein cadaverine</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycoconjugates</topic><topic>Hydrogen-Ion Concentration</topic><topic>Inhibition</topic><topic>IodoA</topic><topic>iodoacetamide</topic><topic>Iodoacetamide - pharmacology</topic><topic>Leishmania</topic><topic>Leishmania - drug effects</topic><topic>Leishmania - enzymology</topic><topic>Leishmania - growth & development</topic><topic>Leishmania infantum - drug effects</topic><topic>Leishmania infantum - enzymology</topic><topic>Leishmania infantum - growth & development</topic><topic>Leishmania major - drug effects</topic><topic>Leishmania major - enzymology</topic><topic>Leishmania major - growth & development</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmania mexicana - enzymology</topic><topic>Leishmania mexicana - growth & development</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>macrophage</topic><topic>Macrophages - enzymology</topic><topic>MDC</topic><topic>MES</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>monodansylcadaverine</topic><topic>Parasite</topic><topic>posttranslational modification</topic><topic>Promastigote</topic><topic>Protozoa</topic><topic>PTM</topic><topic>Temperature</topic><topic>TGase</topic><topic>transglutaminase</topic><topic>Transglutaminase (EC 2.3.2.13)</topic><topic>Transglutaminases - analysis</topic><topic>Transglutaminases - antagonists & inhibitors</topic><topic>Transglutaminases - physiology</topic><topic>Trypanosomatid</topic><topic>Western blot</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brobey, Reynolds K.B.</creatorcontrib><creatorcontrib>Soong, Lynn</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brobey, Reynolds K.B.</au><au>Soong, Lynn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>114</volume><issue>2</issue><spage>94</spage><epage>102</epage><pages>94-102</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether
Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in
Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In
L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37–55
°C) than that in promastigote lysates.
Leishmania TGase differs from mouse macrophage (MΦ) TGase in two ways: (1) the parasite enzyme is Ca
2+-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for
L. amazonensis TGase were found within the 50–75
kDa region, while those for the MΦ TGase were located within 37–50
kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for
L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>16620812</pmid><doi>10.1016/j.exppara.2006.02.021</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Experimental parasitology, 2006-10, Vol.114 (2), p.94-102 |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | 2-[ N-morpholino]ethanesulfonic acid Amastigote Animals BCA bicinchonic acid Biological and medical sciences Blotting, Western Cadaverine - analogs & derivatives Cadaverine - pharmacology Cells, Cultured Colorimetry cystamine Cystamine - pharmacology DDC didansylcadaverine Enzyme Inhibitors - pharmacology fluorescein cadaverine Fundamental and applied biological sciences. Psychology Glycoconjugates Hydrogen-Ion Concentration Inhibition IodoA iodoacetamide Iodoacetamide - pharmacology Leishmania Leishmania - drug effects Leishmania - enzymology Leishmania - growth & development Leishmania infantum - drug effects Leishmania infantum - enzymology Leishmania infantum - growth & development Leishmania major - drug effects Leishmania major - enzymology Leishmania major - growth & development Leishmania mexicana - drug effects Leishmania mexicana - enzymology Leishmania mexicana - growth & development Life cycle. Host-agent relationship. Pathogenesis macrophage Macrophages - enzymology MDC MES Mice Mice, Inbred BALB C monodansylcadaverine Parasite posttranslational modification Promastigote Protozoa PTM Temperature TGase transglutaminase Transglutaminase (EC 2.3.2.13) Transglutaminases - analysis Transglutaminases - antagonists & inhibitors Transglutaminases - physiology Trypanosomatid Western blot |
| title | Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation |
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