Effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania
Polyamine biosynthesis was studied in wild-type promastigotes of Leishmania donovani and Leishmania amazonensis treated with pentamidine and in the parasites resistant to this drug. Treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, or...
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| Veröffentlicht in: | Experimental parasitology 1997-03, Vol.85 (3), p.274-282 |
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| creator | BASSELIN, M BADET-DENISOT, M.-A LAWRENCE, F ROBERT-GERO, M |
| description | Polyamine biosynthesis was studied in wild-type promastigotes of Leishmania donovani and Leishmania amazonensis treated with pentamidine and in the parasites resistant to this drug. Treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, ornithine, and putrescine pools, while the level of intracellular spermidine remained unchanged. In these cells, the activity of the enzyme ornithine decarboxylase was found to be decreased. Compared to wild-type cells, resistant clones had a lower level of putrescine, higher pools of arginine and ornithine, and a similar spermidine content. Analysis by Western blot and DFMO-binding showed reduced amount of ornithine decarboxylase. Furthermore, in the resistant cells, the kinetic parameters of the enzyme spermidine synthase were markedly changed, showing increased affinity to putrescine and decreased affinity to pentamidine. Thus, it seems that polyamine biosynthesis pathway is a target of pentamidine in Leishmania and is altered in resistant clones. |
| doi_str_mv | 10.1006/expr.1996.4131 |
| format | Article |
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Treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, ornithine, and putrescine pools, while the level of intracellular spermidine remained unchanged. In these cells, the activity of the enzyme ornithine decarboxylase was found to be decreased. Compared to wild-type cells, resistant clones had a lower level of putrescine, higher pools of arginine and ornithine, and a similar spermidine content. Analysis by Western blot and DFMO-binding showed reduced amount of ornithine decarboxylase. Furthermore, in the resistant cells, the kinetic parameters of the enzyme spermidine synthase were markedly changed, showing increased affinity to putrescine and decreased affinity to pentamidine. Thus, it seems that polyamine biosynthesis pathway is a target of pentamidine in Leishmania and is altered in resistant clones.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1006/expr.1996.4131</identifier><identifier>PMID: 9085924</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>San Diego, CA: Elsevier</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiparasitic agents ; Biological and medical sciences ; Blotting, Western ; Chromatography, High Pressure Liquid ; Drug Resistance ; Eflornithine - metabolism ; Eflornithine - pharmacology ; Enzyme Inhibitors - metabolism ; Enzyme Inhibitors - pharmacology ; Leishmania amazonensis ; Leishmania donovani ; Leishmania donovani - drug effects ; Leishmania donovani - enzymology ; Leishmania donovani - metabolism ; Leishmania mexicana - drug effects ; Leishmania mexicana - enzymology ; Leishmania mexicana - metabolism ; Medical sciences ; Ornithine Decarboxylase - metabolism ; Ornithine Decarboxylase Inhibitors ; Pentamidine - pharmacology ; Pharmacology. Drug treatments ; Polyamines - analysis ; Spermidine Synthase - antagonists & inhibitors ; Spermidine Synthase - metabolism ; Trypanocidal Agents - pharmacology</subject><ispartof>Experimental parasitology, 1997-03, Vol.85 (3), p.274-282</ispartof><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2625212$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9085924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BASSELIN, M</creatorcontrib><creatorcontrib>BADET-DENISOT, M.-A</creatorcontrib><creatorcontrib>LAWRENCE, F</creatorcontrib><creatorcontrib>ROBERT-GERO, M</creatorcontrib><title>Effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Polyamine biosynthesis was studied in wild-type promastigotes of Leishmania donovani and Leishmania amazonensis treated with pentamidine and in the parasites resistant to this drug. Treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, ornithine, and putrescine pools, while the level of intracellular spermidine remained unchanged. In these cells, the activity of the enzyme ornithine decarboxylase was found to be decreased. Compared to wild-type cells, resistant clones had a lower level of putrescine, higher pools of arginine and ornithine, and a similar spermidine content. Analysis by Western blot and DFMO-binding showed reduced amount of ornithine decarboxylase. Furthermore, in the resistant cells, the kinetic parameters of the enzyme spermidine synthase were markedly changed, showing increased affinity to putrescine and decreased affinity to pentamidine. Thus, it seems that polyamine biosynthesis pathway is a target of pentamidine in Leishmania and is altered in resistant clones.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Drug Resistance</subject><subject>Eflornithine - metabolism</subject><subject>Eflornithine - pharmacology</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Leishmania amazonensis</subject><subject>Leishmania donovani</subject><subject>Leishmania donovani - drug effects</subject><subject>Leishmania donovani - enzymology</subject><subject>Leishmania donovani - metabolism</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - enzymology</subject><subject>Leishmania mexicana - metabolism</subject><subject>Medical sciences</subject><subject>Ornithine Decarboxylase - metabolism</subject><subject>Ornithine Decarboxylase Inhibitors</subject><subject>Pentamidine - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyamines - analysis</subject><subject>Spermidine Synthase - antagonists & inhibitors</subject><subject>Spermidine Synthase - metabolism</subject><subject>Trypanocidal Agents - pharmacology</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAUhS0EgvJY2ZA8ICZSrh-J7RFVvKRKLDBXTnwtjBInxC7QlV9OgQqxMV0dfd85wyXkmMGUAVQX-D6MU2ZMNZVMsC0yYWCg4FKabTIBYLKQ2sg9sp_SMwBoxuUu2TWgS8PlhHxceY9NTrT3dMCYbRdciEj7SIe-Xa3jOrT4ii210dE69GkV8xOmkGiI9C20rsirAc__tos8os3ozr87f8H4Vcw2ZjrHkJ46G4M9JDvetgmPNveAPF5fPcxui_n9zd3scl4MvKpyoW2lFNSgeG1EYwUiVgYa3ZTSezC156Wzdc01CKcRGhC6FJorrX3lHXfigJz97A5j_7LElBddSA22rY3YL9NCacMUaPWvyBRjXJViLZ5sxGXdoVsMY-jsuFpsvrvmpxtuU2NbP9rYhPSr8YqXnHHxCdrTi60</recordid><startdate>19970301</startdate><enddate>19970301</enddate><creator>BASSELIN, M</creator><creator>BADET-DENISOT, M.-A</creator><creator>LAWRENCE, F</creator><creator>ROBERT-GERO, M</creator><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>M7N</scope><scope>7X8</scope></search><sort><creationdate>19970301</creationdate><title>Effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania</title><author>BASSELIN, M ; BADET-DENISOT, M.-A ; LAWRENCE, F ; ROBERT-GERO, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p266t-8a6770b072b93ca3eee690c8c54ff09bf25dabb2803d8e0c0385382788f6fd2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Drug Resistance</topic><topic>Eflornithine - metabolism</topic><topic>Eflornithine - pharmacology</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Leishmania amazonensis</topic><topic>Leishmania donovani</topic><topic>Leishmania donovani - drug effects</topic><topic>Leishmania donovani - enzymology</topic><topic>Leishmania donovani - metabolism</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmania mexicana - enzymology</topic><topic>Leishmania mexicana - metabolism</topic><topic>Medical sciences</topic><topic>Ornithine Decarboxylase - metabolism</topic><topic>Ornithine Decarboxylase Inhibitors</topic><topic>Pentamidine - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyamines - analysis</topic><topic>Spermidine Synthase - antagonists & inhibitors</topic><topic>Spermidine Synthase - metabolism</topic><topic>Trypanocidal Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BASSELIN, M</creatorcontrib><creatorcontrib>BADET-DENISOT, M.-A</creatorcontrib><creatorcontrib>LAWRENCE, F</creatorcontrib><creatorcontrib>ROBERT-GERO, M</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>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>BASSELIN, M</au><au>BADET-DENISOT, M.-A</au><au>LAWRENCE, F</au><au>ROBERT-GERO, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>1997-03-01</date><risdate>1997</risdate><volume>85</volume><issue>3</issue><spage>274</spage><epage>282</epage><pages>274-282</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>Polyamine biosynthesis was studied in wild-type promastigotes of Leishmania donovani and Leishmania amazonensis treated with pentamidine and in the parasites resistant to this drug. Treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, ornithine, and putrescine pools, while the level of intracellular spermidine remained unchanged. In these cells, the activity of the enzyme ornithine decarboxylase was found to be decreased. Compared to wild-type cells, resistant clones had a lower level of putrescine, higher pools of arginine and ornithine, and a similar spermidine content. Analysis by Western blot and DFMO-binding showed reduced amount of ornithine decarboxylase. Furthermore, in the resistant cells, the kinetic parameters of the enzyme spermidine synthase were markedly changed, showing increased affinity to putrescine and decreased affinity to pentamidine. Thus, it seems that polyamine biosynthesis pathway is a target of pentamidine in Leishmania and is altered in resistant clones.</abstract><cop>San Diego, CA</cop><pub>Elsevier</pub><pmid>9085924</pmid><doi>10.1006/expr.1996.4131</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Biological and medical sciences Blotting, Western Chromatography, High Pressure Liquid Drug Resistance Eflornithine - metabolism Eflornithine - pharmacology Enzyme Inhibitors - metabolism Enzyme Inhibitors - pharmacology Leishmania amazonensis Leishmania donovani Leishmania donovani - drug effects Leishmania donovani - enzymology Leishmania donovani - metabolism Leishmania mexicana - drug effects Leishmania mexicana - enzymology Leishmania mexicana - metabolism Medical sciences Ornithine Decarboxylase - metabolism Ornithine Decarboxylase Inhibitors Pentamidine - pharmacology Pharmacology. Drug treatments Polyamines - analysis Spermidine Synthase - antagonists & inhibitors Spermidine Synthase - metabolism Trypanocidal Agents - pharmacology |
| title | Effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania |
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