Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes
Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil 1 Setor de Microscopia Eletrônica e Departamento de Microbiol...
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| Veröffentlicht in: | Microbiology (Society for General Microbiology) 1999-11, Vol.145 (11), p.3213-3220 |
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| creator | Vannier-Santos, Marcos A Martiny, Andrea Lins, Ulysses Urbina, Julio A Borges, Valeria M de Souza, Wanderley |
| description | Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil 1
Setor de Microscopia Eletrônica e Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil 2
Laboratório de Química Biológica, Instituto Venezoelano de Investigaciones Científicas-IVIC, Venezuela 3
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil 4
Author for correspondence: Marcos A. Vannier-Santos. Tel: +55 21 260 6963. Fax: +55 21 280 8193. e-mail: vannier{at}biof.ufrj.br
The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
Keywords: sterol biosynthesis inhibitors, ketoconazole, terbinafine, acidocalcisome, Leishmania Abbreviations: ER, endoplasmic reticulum; ESI, electron spectroscopic imaging; SBI, sterol biosynthesis inhibitors |
| doi_str_mv | 10.1099/00221287-145-11-3213 |
| format | Article |
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Setor de Microscopia Eletrônica e Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil 2
Laboratório de Química Biológica, Instituto Venezoelano de Investigaciones Científicas-IVIC, Venezuela 3
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil 4
Author for correspondence: Marcos A. Vannier-Santos. Tel: +55 21 260 6963. Fax: +55 21 280 8193. e-mail: vannier{at}biof.ufrj.br
The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
Keywords: sterol biosynthesis inhibitors, ketoconazole, terbinafine, acidocalcisome, Leishmania Abbreviations: ER, endoplasmic reticulum; ESI, electron spectroscopic imaging; SBI, sterol biosynthesis inhibitors</description><identifier>ISSN: 1350-0872</identifier><identifier>EISSN: 1465-2080</identifier><identifier>DOI: 10.1099/00221287-145-11-3213</identifier><identifier>PMID: 10589730</identifier><language>eng</language><publisher>Reading: Soc General Microbiol</publisher><subject>acidocalcisomes ; Animals ; Biochemistry. Physiology. Immunology. Molecular biology ; Biological and medical sciences ; Calcium - metabolism ; Cricetinae ; Cystatin C ; Cystatins - analysis ; Electron Probe Microanalysis ; Fundamental and applied biological sciences. Psychology ; Horseradish Peroxidase - analysis ; Humans ; Inclusion Bodies - chemistry ; Inclusion Bodies - metabolism ; Inclusion Bodies - ultrastructure ; Ketoconazole - pharmacology ; Leishmania acidocalcisomes ; Leishmania amazonensis ; Leishmania mexicana - drug effects ; Leishmania mexicana - metabolism ; Leishmania mexicana - ultrastructure ; Microscopy, Electron ; Naphthalenes - pharmacology ; Phosphorus - metabolism ; Protozoa ; sterols ; Sterols - antagonists & inhibitors ; Sterols - biosynthesis ; Terbinafine ; Transferrin - analysis ; Trypanocidal Agents - pharmacology</subject><ispartof>Microbiology (Society for General Microbiology), 1999-11, Vol.145 (11), p.3213-3220</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-b5b498c995495454d7b68972c65c1b79e90bf9efcc9a6c78256d04ea2ac06dcd3</citedby><cites>FETCH-LOGICAL-c510t-b5b498c995495454d7b68972c65c1b79e90bf9efcc9a6c78256d04ea2ac06dcd3</cites></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=1209214$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10589730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vannier-Santos, Marcos A</creatorcontrib><creatorcontrib>Martiny, Andrea</creatorcontrib><creatorcontrib>Lins, Ulysses</creatorcontrib><creatorcontrib>Urbina, Julio A</creatorcontrib><creatorcontrib>Borges, Valeria M</creatorcontrib><creatorcontrib>de Souza, Wanderley</creatorcontrib><title>Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes</title><title>Microbiology (Society for General Microbiology)</title><addtitle>Microbiology</addtitle><description>Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil 1
Setor de Microscopia Eletrônica e Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil 2
Laboratório de Química Biológica, Instituto Venezoelano de Investigaciones Científicas-IVIC, Venezuela 3
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil 4
Author for correspondence: Marcos A. Vannier-Santos. Tel: +55 21 260 6963. Fax: +55 21 280 8193. e-mail: vannier{at}biof.ufrj.br
The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
Keywords: sterol biosynthesis inhibitors, ketoconazole, terbinafine, acidocalcisome, Leishmania Abbreviations: ER, endoplasmic reticulum; ESI, electron spectroscopic imaging; SBI, sterol biosynthesis inhibitors</description><subject>acidocalcisomes</subject><subject>Animals</subject><subject>Biochemistry. Physiology. Immunology. Molecular biology</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cricetinae</subject><subject>Cystatin C</subject><subject>Cystatins - analysis</subject><subject>Electron Probe Microanalysis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Horseradish Peroxidase - analysis</subject><subject>Humans</subject><subject>Inclusion Bodies - chemistry</subject><subject>Inclusion Bodies - metabolism</subject><subject>Inclusion Bodies - ultrastructure</subject><subject>Ketoconazole - pharmacology</subject><subject>Leishmania acidocalcisomes</subject><subject>Leishmania amazonensis</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - metabolism</subject><subject>Leishmania mexicana - ultrastructure</subject><subject>Microscopy, Electron</subject><subject>Naphthalenes - pharmacology</subject><subject>Phosphorus - metabolism</subject><subject>Protozoa</subject><subject>sterols</subject><subject>Sterols - antagonists & inhibitors</subject><subject>Sterols - biosynthesis</subject><subject>Terbinafine</subject><subject>Transferrin - analysis</subject><subject>Trypanocidal Agents - pharmacology</subject><issn>1350-0872</issn><issn>1465-2080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV-L1TAQxYMo7rr6DUTyID4I1UnatMmjLP5ZuOCLPoc0nW4jTXLNtMh-e7PeK-6bkJDA_GbmcA5jLwW8E2DMewAphdRDIzrVCNG0UrSP2KXoetVI0PC4_lsFDehBXrBnRD8AahHEU3YhQGkztHDJ1pt4dKFETBvPM6cNS175GDLdpW1BCsRXdBPxLfPjkqneshN3aeLerT7skTvv97ivbgs58ZD4AQMt0aXgailM-Q9HOSI9Z09mtxK-OL9X7Punj9-uvzSHr59vrj8cGq8EbM2oxs5ob4zq6lHdNIx9lSt9r7wYB4MGxtng7L1xvR-0VP0EHTrpPPSTn9or9uY091jyzx1pszGQx3V1CfNOtjdta6oF_wXFoLRutaxgdwJ9yUQFZ3ssIbpyZwXY-zjs3zhsjcMKYe_jqG2vzvP3MeL0oOnkfwVenwFH1ae5uFS9-sdJMFJ0FXt7wpZwu_wKBe0tphiqmJpU1ewfLv0NlSmijg</recordid><startdate>19991101</startdate><enddate>19991101</enddate><creator>Vannier-Santos, Marcos A</creator><creator>Martiny, Andrea</creator><creator>Lins, Ulysses</creator><creator>Urbina, Julio A</creator><creator>Borges, Valeria M</creator><creator>de Souza, Wanderley</creator><general>Soc General Microbiol</general><general>Society for General Microbiology</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>7QP</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>19991101</creationdate><title>Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes</title><author>Vannier-Santos, Marcos A ; Martiny, Andrea ; Lins, Ulysses ; Urbina, Julio A ; Borges, Valeria M ; de Souza, Wanderley</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-b5b498c995495454d7b68972c65c1b79e90bf9efcc9a6c78256d04ea2ac06dcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>acidocalcisomes</topic><topic>Animals</topic><topic>Biochemistry. Physiology. Immunology. Molecular biology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cricetinae</topic><topic>Cystatin C</topic><topic>Cystatins - analysis</topic><topic>Electron Probe Microanalysis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Horseradish Peroxidase - analysis</topic><topic>Humans</topic><topic>Inclusion Bodies - chemistry</topic><topic>Inclusion Bodies - metabolism</topic><topic>Inclusion Bodies - ultrastructure</topic><topic>Ketoconazole - pharmacology</topic><topic>Leishmania acidocalcisomes</topic><topic>Leishmania amazonensis</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmania mexicana - metabolism</topic><topic>Leishmania mexicana - ultrastructure</topic><topic>Microscopy, Electron</topic><topic>Naphthalenes - pharmacology</topic><topic>Phosphorus - metabolism</topic><topic>Protozoa</topic><topic>sterols</topic><topic>Sterols - antagonists & inhibitors</topic><topic>Sterols - biosynthesis</topic><topic>Terbinafine</topic><topic>Transferrin - analysis</topic><topic>Trypanocidal Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vannier-Santos, Marcos A</creatorcontrib><creatorcontrib>Martiny, Andrea</creatorcontrib><creatorcontrib>Lins, Ulysses</creatorcontrib><creatorcontrib>Urbina, Julio A</creatorcontrib><creatorcontrib>Borges, Valeria M</creatorcontrib><creatorcontrib>de Souza, Wanderley</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>Calcium & Calcified Tissue Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Microbiology (Society for General Microbiology)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vannier-Santos, Marcos A</au><au>Martiny, Andrea</au><au>Lins, Ulysses</au><au>Urbina, Julio A</au><au>Borges, Valeria M</au><au>de Souza, Wanderley</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes</atitle><jtitle>Microbiology (Society for General Microbiology)</jtitle><addtitle>Microbiology</addtitle><date>1999-11-01</date><risdate>1999</risdate><volume>145</volume><issue>11</issue><spage>3213</spage><epage>3220</epage><pages>3213-3220</pages><issn>1350-0872</issn><eissn>1465-2080</eissn><abstract>Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil 1
Setor de Microscopia Eletrônica e Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil 2
Laboratório de Química Biológica, Instituto Venezoelano de Investigaciones Científicas-IVIC, Venezuela 3
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil 4
Author for correspondence: Marcos A. Vannier-Santos. Tel: +55 21 260 6963. Fax: +55 21 280 8193. e-mail: vannier{at}biof.ufrj.br
The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
Keywords: sterol biosynthesis inhibitors, ketoconazole, terbinafine, acidocalcisome, Leishmania Abbreviations: ER, endoplasmic reticulum; ESI, electron spectroscopic imaging; SBI, sterol biosynthesis inhibitors</abstract><cop>Reading</cop><pub>Soc General Microbiol</pub><pmid>10589730</pmid><doi>10.1099/00221287-145-11-3213</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | acidocalcisomes Animals Biochemistry. Physiology. Immunology. Molecular biology Biological and medical sciences Calcium - metabolism Cricetinae Cystatin C Cystatins - analysis Electron Probe Microanalysis Fundamental and applied biological sciences. Psychology Horseradish Peroxidase - analysis Humans Inclusion Bodies - chemistry Inclusion Bodies - metabolism Inclusion Bodies - ultrastructure Ketoconazole - pharmacology Leishmania acidocalcisomes Leishmania amazonensis Leishmania mexicana - drug effects Leishmania mexicana - metabolism Leishmania mexicana - ultrastructure Microscopy, Electron Naphthalenes - pharmacology Phosphorus - metabolism Protozoa sterols Sterols - antagonists & inhibitors Sterols - biosynthesis Terbinafine Transferrin - analysis Trypanocidal Agents - pharmacology |
| title | Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes |
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