Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes
The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we anal...
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| Veröffentlicht in: | Parasitology 2018-09, Vol.145 (10), p.1304-1310 |
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| creator | Rebello, Karina M. Andrade-Neto, Valter V. Zuma, Aline A. Motta, Maria Cristina M. Gomes, Claudia Regina B. de Souza, Marcus Vinícius N. Atella, Geórgia C. Branquinha, Marta H. Santos, André L. S. Torres-Santos, Eduardo Caio d'Avila-Levy, Claudia M. |
| description | The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite. |
| doi_str_mv | 10.1017/S0031182018000823 |
| format | Article |
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S. ; Torres-Santos, Eduardo Caio ; d'Avila-Levy, Claudia M.</creator><creatorcontrib>Rebello, Karina M. ; Andrade-Neto, Valter V. ; Zuma, Aline A. ; Motta, Maria Cristina M. ; Gomes, Claudia Regina B. ; de Souza, Marcus Vinícius N. ; Atella, Geórgia C. ; Branquinha, Marta H. ; Santos, André L. S. ; Torres-Santos, Eduardo Caio ; d'Avila-Levy, Claudia M.</creatorcontrib><description>The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.</description><identifier>ISSN: 0031-1820</identifier><identifier>EISSN: 1469-8161</identifier><identifier>DOI: 10.1017/S0031182018000823</identifier><identifier>PMID: 29806577</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Accumulation ; Antiretroviral drugs ; Biosynthesis ; Cholesterol ; Cholesterol - analysis ; Chromatography, Thin Layer ; Esters ; Fluorescence ; Fluorescence microscopy ; Gas chromatography ; Gas Chromatography-Mass Spectrometry ; HIV ; HIV Protease Inhibitors - pharmacology ; Human immunodeficiency virus ; Leishmania amazonensis ; Leishmania mexicana - drug effects ; Leishmania mexicana - ultrastructure ; Lipid composition ; Lipid metabolism ; Lipid Metabolism - drug effects ; Lipids ; Lipids - analysis ; Lipophilic ; Lopinavir ; Lopinavir - pharmacology ; Mass spectrometry ; Mass spectroscopy ; Metabolism ; Microscopy, Electron, Transmission ; Mode of action ; Morphology ; Parasites ; Parasitic diseases ; Patients ; Penicillin ; Peptidase ; Promastigotes ; Special Issue ; Special Issue Research Article ; Spectrofluorimetry ; Sterols ; Sterols - analysis ; Thin layer chromatography ; Transmission electron microscopy ; Tropical diseases ; Ultrastructure</subject><ispartof>Parasitology, 2018-09, Vol.145 (10), p.1304-1310</ispartof><rights>Copyright © Cambridge University Press 2018</rights><rights>Copyright © Cambridge University Press 2018 This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (the “License”) (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Cambridge University Press 2018 2018 Cambridge University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-ac9bb2f31c9f8252b967f3f16908d5f35f67824133b91364e4b6a2d8fda62543</citedby><cites>FETCH-LOGICAL-c428t-ac9bb2f31c9f8252b967f3f16908d5f35f67824133b91364e4b6a2d8fda62543</cites><orcidid>0000-0001-8042-4695</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0031182018000823/type/journal_article$$EHTML$$P50$$Gcambridge$$Hfree_for_read</linktohtml><link.rule.ids>164,230,314,776,780,881,27903,27904,55607</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29806577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rebello, Karina M.</creatorcontrib><creatorcontrib>Andrade-Neto, Valter V.</creatorcontrib><creatorcontrib>Zuma, Aline A.</creatorcontrib><creatorcontrib>Motta, Maria Cristina M.</creatorcontrib><creatorcontrib>Gomes, Claudia Regina B.</creatorcontrib><creatorcontrib>de Souza, Marcus Vinícius N.</creatorcontrib><creatorcontrib>Atella, Geórgia C.</creatorcontrib><creatorcontrib>Branquinha, Marta H.</creatorcontrib><creatorcontrib>Santos, André L. S.</creatorcontrib><creatorcontrib>Torres-Santos, Eduardo Caio</creatorcontrib><creatorcontrib>d'Avila-Levy, Claudia M.</creatorcontrib><title>Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes</title><title>Parasitology</title><addtitle>Parasitology</addtitle><description>The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.</description><subject>Accumulation</subject><subject>Antiretroviral drugs</subject><subject>Biosynthesis</subject><subject>Cholesterol</subject><subject>Cholesterol - analysis</subject><subject>Chromatography, Thin Layer</subject><subject>Esters</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Gas chromatography</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>HIV</subject><subject>HIV Protease Inhibitors - pharmacology</subject><subject>Human immunodeficiency virus</subject><subject>Leishmania amazonensis</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - ultrastructure</subject><subject>Lipid composition</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Lipids</subject><subject>Lipids - analysis</subject><subject>Lipophilic</subject><subject>Lopinavir</subject><subject>Lopinavir - pharmacology</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Microscopy, Electron, Transmission</subject><subject>Mode of action</subject><subject>Morphology</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Patients</subject><subject>Penicillin</subject><subject>Peptidase</subject><subject>Promastigotes</subject><subject>Special Issue</subject><subject>Special Issue Research Article</subject><subject>Spectrofluorimetry</subject><subject>Sterols</subject><subject>Sterols - analysis</subject><subject>Thin layer chromatography</subject><subject>Transmission electron microscopy</subject><subject>Tropical diseases</subject><subject>Ultrastructure</subject><issn>0031-1820</issn><issn>1469-8161</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>IKXGN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kU2L1TAUhosoznX0B7iRgBsXVnOSNk02ggwzzsAFFw5uy2mb3HuGNqlJOqD-eXuZ6_iFEMjifc6THN6ieA78DXBo3n7iXAJowUFzzrWQD4oNVMqUGhQ8LDaHuDzkJ8WTlG5WRkklHhcnwmiu6qbZFN-3YSaPtxRfM_Ts8upzCWy2c6YBk2Xk99RRDmtKflh6mxiO2UbMFDxbT95bNtJMA5tsxi6MlCYWHNtaSvsJPSHDCb8Fb32ixOYYJkyZdiHb9LR45HBM9tnxPi2uL86vzy7L7ccPV2fvt2VfCZ1L7E3XCSehN06LWnRGNU46UIbroXaydqrRogIpOwNSVbbqFIpBuwGVqCt5Wry7085LN9mhtz5HHNs50oTxaxuQ2j8TT_t2F25bBbKRjV4Fr46CGL4sNuV2otTbcURvw5JawSvFoQIjV_TlX-hNWKJft1sp00gDjTkI4Y7qY0gpWnf_GeDtodn2n2bXmRe_b3E_8bPKFZBHKU5dpGFnf739f-0PgXuvCw</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Rebello, Karina M.</creator><creator>Andrade-Neto, Valter V.</creator><creator>Zuma, Aline A.</creator><creator>Motta, Maria Cristina M.</creator><creator>Gomes, Claudia Regina B.</creator><creator>de Souza, Marcus Vinícius N.</creator><creator>Atella, Geórgia C.</creator><creator>Branquinha, Marta H.</creator><creator>Santos, André L. 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S.</creatorcontrib><creatorcontrib>Torres-Santos, Eduardo Caio</creatorcontrib><creatorcontrib>d'Avila-Levy, Claudia M.</creatorcontrib><collection>Cambridge University Press Wholly Gold Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rebello, Karina M.</au><au>Andrade-Neto, Valter V.</au><au>Zuma, Aline A.</au><au>Motta, Maria Cristina M.</au><au>Gomes, Claudia Regina B.</au><au>de Souza, Marcus Vinícius N.</au><au>Atella, Geórgia C.</au><au>Branquinha, Marta H.</au><au>Santos, André L. S.</au><au>Torres-Santos, Eduardo Caio</au><au>d'Avila-Levy, Claudia M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes</atitle><jtitle>Parasitology</jtitle><addtitle>Parasitology</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>145</volume><issue>10</issue><spage>1304</spage><epage>1310</epage><pages>1304-1310</pages><issn>0031-1820</issn><eissn>1469-8161</eissn><abstract>The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>29806577</pmid><doi>10.1017/S0031182018000823</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8042-4695</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Parasitology, 2018-09, Vol.145 (10), p.1304-1310 |
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| subjects | Accumulation Antiretroviral drugs Biosynthesis Cholesterol Cholesterol - analysis Chromatography, Thin Layer Esters Fluorescence Fluorescence microscopy Gas chromatography Gas Chromatography-Mass Spectrometry HIV HIV Protease Inhibitors - pharmacology Human immunodeficiency virus Leishmania amazonensis Leishmania mexicana - drug effects Leishmania mexicana - ultrastructure Lipid composition Lipid metabolism Lipid Metabolism - drug effects Lipids Lipids - analysis Lipophilic Lopinavir Lopinavir - pharmacology Mass spectrometry Mass spectroscopy Metabolism Microscopy, Electron, Transmission Mode of action Morphology Parasites Parasitic diseases Patients Penicillin Peptidase Promastigotes Special Issue Special Issue Research Article Spectrofluorimetry Sterols Sterols - analysis Thin layer chromatography Transmission electron microscopy Tropical diseases Ultrastructure |
| title | Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes |
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