Effects of the lipophilic biscation, bis-Pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria
In order to further investigate the mechanism of action of bridged lipophilic bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini et al., Biochem Pharmacol 53: 1543–1552, 1997), we studied the effects...
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creator | Moreno, Giuliana Nocentini, Silvano Guggiari, Michèle Salet, Christian |
description | In order to further investigate the mechanism of action of bridged lipophilic
bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini
et al.,
Biochem Pharmacol 53: 1543–1552, 1997), we studied the effects of a
bis-pyridinium oxime with a polymethylene chain N = 12 (BP12) on isolated rat liver mitochondria. Respiration in the absence of ADP with succinate plus rotenone as substrate was not affected after treatment with various concentrations of BP12 up to 10 μM, while the ADP-stimulated respiration was slowed down, with a parallel decrease in ATP synthesis. No effects of BP12 were detected on membrane potential, ATPase activity, and inorganic phosphate transport, but the adenine nucleotide translocase was inactivated and a permeability transition of the inner membrane was induced in the presence of calcium. These data suggest that mitochondrial impairment of ATP synthesis and the formation of the permeability transition pore may be responsible for apoptotic cell death already observed in cells treated with BP12. |
doi_str_mv | 10.1016/S0006-2952(99)00318-4 |
format | Article |
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bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini
et al.,
Biochem Pharmacol 53: 1543–1552, 1997), we studied the effects of a
bis-pyridinium oxime with a polymethylene chain N = 12 (BP12) on isolated rat liver mitochondria. Respiration in the absence of ADP with succinate plus rotenone as substrate was not affected after treatment with various concentrations of BP12 up to 10 μM, while the ADP-stimulated respiration was slowed down, with a parallel decrease in ATP synthesis. No effects of BP12 were detected on membrane potential, ATPase activity, and inorganic phosphate transport, but the adenine nucleotide translocase was inactivated and a permeability transition of the inner membrane was induced in the presence of calcium. These data suggest that mitochondrial impairment of ATP synthesis and the formation of the permeability transition pore may be responsible for apoptotic cell death already observed in cells treated with BP12.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/S0006-2952(99)00318-4</identifier><identifier>PMID: 10609554</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenosine Triphosphate - biosynthesis ; Animals ; Apoptosis ; Biological and medical sciences ; bis-pyridinium oxime ; Cell physiology ; Cell Respiration - drug effects ; Effects of physical and chemical agents ; Energy Metabolism - drug effects ; Fundamental and applied biological sciences. Psychology ; In Vitro Techniques ; Intracellular Membranes - drug effects ; Intracellular Membranes - metabolism ; mitochondria ; Mitochondria, Liver - drug effects ; Mitochondria, Liver - metabolism ; Molecular and cellular biology ; Oxidative Phosphorylation ; Oximes - pharmacology ; Permeability - drug effects ; Pyridinium Compounds - pharmacology ; Rats</subject><ispartof>Biochemical pharmacology, 2000-02, Vol.59 (3), p.261-266</ispartof><rights>2000 Elsevier Science Inc.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-b7f048f4559eea76efbcdf1b1769e60d87ec94bbc5d26391be4bda360276df513</citedby><cites>FETCH-LOGICAL-c390t-b7f048f4559eea76efbcdf1b1769e60d87ec94bbc5d26391be4bda360276df513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-2952(99)00318-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1225251$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10609554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moreno, Giuliana</creatorcontrib><creatorcontrib>Nocentini, Silvano</creatorcontrib><creatorcontrib>Guggiari, Michèle</creatorcontrib><creatorcontrib>Salet, Christian</creatorcontrib><title>Effects of the lipophilic biscation, bis-Pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>In order to further investigate the mechanism of action of bridged lipophilic
bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini
et al.,
Biochem Pharmacol 53: 1543–1552, 1997), we studied the effects of a
bis-pyridinium oxime with a polymethylene chain N = 12 (BP12) on isolated rat liver mitochondria. Respiration in the absence of ADP with succinate plus rotenone as substrate was not affected after treatment with various concentrations of BP12 up to 10 μM, while the ADP-stimulated respiration was slowed down, with a parallel decrease in ATP synthesis. No effects of BP12 were detected on membrane potential, ATPase activity, and inorganic phosphate transport, but the adenine nucleotide translocase was inactivated and a permeability transition of the inner membrane was induced in the presence of calcium. These data suggest that mitochondrial impairment of ATP synthesis and the formation of the permeability transition pore may be responsible for apoptotic cell death already observed in cells treated with BP12.</description><subject>Adenosine Triphosphate - biosynthesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>bis-pyridinium oxime</subject><subject>Cell physiology</subject><subject>Cell Respiration - drug effects</subject><subject>Effects of physical and chemical agents</subject><subject>Energy Metabolism - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Vitro Techniques</subject><subject>Intracellular Membranes - drug effects</subject><subject>Intracellular Membranes - metabolism</subject><subject>mitochondria</subject><subject>Mitochondria, Liver - drug effects</subject><subject>Mitochondria, Liver - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Oxidative Phosphorylation</subject><subject>Oximes - pharmacology</subject><subject>Permeability - drug effects</subject><subject>Pyridinium Compounds - pharmacology</subject><subject>Rats</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-K1TAQxoso7nH1EZRciChsNWmbtLkSXdY_sOCCeh3SZOIZaZOzSSqe1_CJTc85qHdCIJnMbyaT76uqx4y-ZJSJV58ppaJuJG-eS_mC0pYNdXen2rChb8u1GO5Wmz_IWfUgpe9rOAh2vzpjVFDJebepfl05ByYnEhzJWyAT7sJuixMaMmIyOmPwF-uxvtlHtOhxmUn4iTOQtzesuSDBl2wAD_EbZDSJaG8JeruYtXRtu4M4gx5Lz7wnOWqf8JDCslKYdAZLZszBbIO3EfXD6p7TU4JHp_28-vru6svlh_r60_uPl2-ua9NKmuuxd7QbXMe5BNC9ADca69jIeiFBUDv0YGQ3jobbRrSSjdCNVreCNr2wjrP2vHp27LuL4XaBlNVcfgzTpD2EJame9rKhgheQH0ETQ0oRnNpFnHXcK0bVaoY6mKFWpZWU6mCG6krdk9MDyziD_afqqH4Bnp4AXaSeXNHGYPrLNQ1vDoO-PmJQ1PiBEFUyCN6AxVi8Uzbgfyb5DeTpqWg</recordid><startdate>20000201</startdate><enddate>20000201</enddate><creator>Moreno, Giuliana</creator><creator>Nocentini, Silvano</creator><creator>Guggiari, Michèle</creator><creator>Salet, Christian</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>20000201</creationdate><title>Effects of the lipophilic biscation, bis-Pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria</title><author>Moreno, Giuliana ; Nocentini, Silvano ; Guggiari, Michèle ; Salet, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-b7f048f4559eea76efbcdf1b1769e60d87ec94bbc5d26391be4bda360276df513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenosine Triphosphate - biosynthesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>bis-pyridinium oxime</topic><topic>Cell physiology</topic><topic>Cell Respiration - drug effects</topic><topic>Effects of physical and chemical agents</topic><topic>Energy Metabolism - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>Intracellular Membranes - drug effects</topic><topic>Intracellular Membranes - metabolism</topic><topic>mitochondria</topic><topic>Mitochondria, Liver - drug effects</topic><topic>Mitochondria, Liver - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Oxidative Phosphorylation</topic><topic>Oximes - pharmacology</topic><topic>Permeability - drug effects</topic><topic>Pyridinium Compounds - pharmacology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moreno, Giuliana</creatorcontrib><creatorcontrib>Nocentini, Silvano</creatorcontrib><creatorcontrib>Guggiari, Michèle</creatorcontrib><creatorcontrib>Salet, Christian</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>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moreno, Giuliana</au><au>Nocentini, Silvano</au><au>Guggiari, Michèle</au><au>Salet, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the lipophilic biscation, bis-Pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2000-02-01</date><risdate>2000</risdate><volume>59</volume><issue>3</issue><spage>261</spage><epage>266</epage><pages>261-266</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>In order to further investigate the mechanism of action of bridged lipophilic
bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini
et al.,
Biochem Pharmacol 53: 1543–1552, 1997), we studied the effects of a
bis-pyridinium oxime with a polymethylene chain N = 12 (BP12) on isolated rat liver mitochondria. Respiration in the absence of ADP with succinate plus rotenone as substrate was not affected after treatment with various concentrations of BP12 up to 10 μM, while the ADP-stimulated respiration was slowed down, with a parallel decrease in ATP synthesis. No effects of BP12 were detected on membrane potential, ATPase activity, and inorganic phosphate transport, but the adenine nucleotide translocase was inactivated and a permeability transition of the inner membrane was induced in the presence of calcium. These data suggest that mitochondrial impairment of ATP synthesis and the formation of the permeability transition pore may be responsible for apoptotic cell death already observed in cells treated with BP12.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10609554</pmid><doi>10.1016/S0006-2952(99)00318-4</doi><tpages>6</tpages></addata></record> |
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subjects | Adenosine Triphosphate - biosynthesis Animals Apoptosis Biological and medical sciences bis-pyridinium oxime Cell physiology Cell Respiration - drug effects Effects of physical and chemical agents Energy Metabolism - drug effects Fundamental and applied biological sciences. Psychology In Vitro Techniques Intracellular Membranes - drug effects Intracellular Membranes - metabolism mitochondria Mitochondria, Liver - drug effects Mitochondria, Liver - metabolism Molecular and cellular biology Oxidative Phosphorylation Oximes - pharmacology Permeability - drug effects Pyridinium Compounds - pharmacology Rats |
title | Effects of the lipophilic biscation, bis-Pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria |
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