Spontaneous Intermembrane Transfer of Various Cholesterol-Derived Hydroperoxide Species: Kinetic Studies with Model Membranes and Cells
Whereas spontaneous and protein-mediated transfer/exchange of cholesterol (Ch) between membranes has been widely studied, relatively little is known about the translocation of Ch oxidation products, particularly hydroperoxide species (ChOOHs), which can act as cytotoxic prooxidants. A major aim of t...
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| Veröffentlicht in: | Biochemistry (Easton) 2001-12, Vol.40 (48), p.14715-14726 |
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| creator | Vila, Andrew Korytowski, Witold Girotti, Albert W |
| description | Whereas spontaneous and protein-mediated transfer/exchange of cholesterol (Ch) between membranes has been widely studied, relatively little is known about the translocation of Ch oxidation products, particularly hydroperoxide species (ChOOHs), which can act as cytotoxic prooxidants. A major aim of the present study was to examine and compare the intermembrane transfer characteristics of several biologically relevant ChOOH isomers, including singlet oxygen-derived 5α-OOH, 6α-OOH, and 6β-OOH and free radical-derived 7α-OOH and 7β-OOH. These species were generated in [14C]Ch-labeled donor membranes [erythrocyte ghosts or unilamellar DMPC/Ch (1.0:0.8 mol/mol) liposomes] by means of dye-sensitized photoperoxidation. Spontaneous transfer to nonoxidized acceptor membranes (DMPC liposomes or ghosts, respectively) at 37 °C was monitored by thin-layer chromatography with phosphorimaging radiodetection (HPTLC-PI) or liquid chromatography with mercury cathode electrochemical detection [HPLC-EC(Hg)]. The former allowed measurement of total (unresolved) ChOOH along with parent Ch, whereas the latter allowed measurement of individual ChOOHs. Ghost membranes in which ∼4% of the Ch had been peroxidized, giving mainly 5α-OOH, transferred total ChOOH and Ch to liposomes in apparent first-order fashion, the rate constant for ChOOH being ∼65 times greater. Like Ch desorption, ChOOH desorption from donor membranes was found to be rate limiting, and rate varied inversely with size when liposomal donors were used. For individual ChOOHs, rate constant magnitude (7α/7β-OOH > 5α-OOH > 6α-OOH > 6β-OOH) correlated inversely with reverse-phase HPLC retention time, suggesting that faster transfer reflects greater hydrophilicity. Liposome-borne ChOOHs exhibited the same order of toxicity toward COH-BR1 cells, which are deficient in ability to detoxify these peroxides. The prospect of disseminating oxidative cell injury via translocation of ChOOHs and other lipid hydroperoxides is readily apparent from these findings. |
| doi_str_mv | 10.1021/bi011408r |
| format | Article |
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A major aim of the present study was to examine and compare the intermembrane transfer characteristics of several biologically relevant ChOOH isomers, including singlet oxygen-derived 5α-OOH, 6α-OOH, and 6β-OOH and free radical-derived 7α-OOH and 7β-OOH. These species were generated in [14C]Ch-labeled donor membranes [erythrocyte ghosts or unilamellar DMPC/Ch (1.0:0.8 mol/mol) liposomes] by means of dye-sensitized photoperoxidation. Spontaneous transfer to nonoxidized acceptor membranes (DMPC liposomes or ghosts, respectively) at 37 °C was monitored by thin-layer chromatography with phosphorimaging radiodetection (HPTLC-PI) or liquid chromatography with mercury cathode electrochemical detection [HPLC-EC(Hg)]. The former allowed measurement of total (unresolved) ChOOH along with parent Ch, whereas the latter allowed measurement of individual ChOOHs. Ghost membranes in which ∼4% of the Ch had been peroxidized, giving mainly 5α-OOH, transferred total ChOOH and Ch to liposomes in apparent first-order fashion, the rate constant for ChOOH being ∼65 times greater. Like Ch desorption, ChOOH desorption from donor membranes was found to be rate limiting, and rate varied inversely with size when liposomal donors were used. For individual ChOOHs, rate constant magnitude (7α/7β-OOH > 5α-OOH > 6α-OOH > 6β-OOH) correlated inversely with reverse-phase HPLC retention time, suggesting that faster transfer reflects greater hydrophilicity. Liposome-borne ChOOHs exhibited the same order of toxicity toward COH-BR1 cells, which are deficient in ability to detoxify these peroxides. The prospect of disseminating oxidative cell injury via translocation of ChOOHs and other lipid hydroperoxides is readily apparent from these findings.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi011408r</identifier><identifier>PMID: 11724586</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Breast Neoplasms - metabolism ; Cell Membrane - metabolism ; Cell Survival - drug effects ; Cells, Cultured - drug effects ; Cholesterol - analogs & derivatives ; Cholesterol - metabolism ; Chromatography, High Pressure Liquid ; Erythrocytes - metabolism ; Female ; Humans ; Isotope Labeling ; Kinetics ; Light ; Lipid Peroxides - metabolism ; Liposomes - metabolism ; Models, Chemical ; Sterols - chemistry</subject><ispartof>Biochemistry (Easton), 2001-12, Vol.40 (48), p.14715-14726</ispartof><rights>Copyright © 2001 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a349t-fcb6f18fbec23ed8d707d2b8a5728c9e1d6889e22bba336e60acc6cccfe4b3733</citedby><cites>FETCH-LOGICAL-a349t-fcb6f18fbec23ed8d707d2b8a5728c9e1d6889e22bba336e60acc6cccfe4b3733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi011408r$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi011408r$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11724586$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vila, Andrew</creatorcontrib><creatorcontrib>Korytowski, Witold</creatorcontrib><creatorcontrib>Girotti, Albert W</creatorcontrib><title>Spontaneous Intermembrane Transfer of Various Cholesterol-Derived Hydroperoxide Species: Kinetic Studies with Model Membranes and Cells</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>Whereas spontaneous and protein-mediated transfer/exchange of cholesterol (Ch) between membranes has been widely studied, relatively little is known about the translocation of Ch oxidation products, particularly hydroperoxide species (ChOOHs), which can act as cytotoxic prooxidants. A major aim of the present study was to examine and compare the intermembrane transfer characteristics of several biologically relevant ChOOH isomers, including singlet oxygen-derived 5α-OOH, 6α-OOH, and 6β-OOH and free radical-derived 7α-OOH and 7β-OOH. These species were generated in [14C]Ch-labeled donor membranes [erythrocyte ghosts or unilamellar DMPC/Ch (1.0:0.8 mol/mol) liposomes] by means of dye-sensitized photoperoxidation. Spontaneous transfer to nonoxidized acceptor membranes (DMPC liposomes or ghosts, respectively) at 37 °C was monitored by thin-layer chromatography with phosphorimaging radiodetection (HPTLC-PI) or liquid chromatography with mercury cathode electrochemical detection [HPLC-EC(Hg)]. The former allowed measurement of total (unresolved) ChOOH along with parent Ch, whereas the latter allowed measurement of individual ChOOHs. Ghost membranes in which ∼4% of the Ch had been peroxidized, giving mainly 5α-OOH, transferred total ChOOH and Ch to liposomes in apparent first-order fashion, the rate constant for ChOOH being ∼65 times greater. Like Ch desorption, ChOOH desorption from donor membranes was found to be rate limiting, and rate varied inversely with size when liposomal donors were used. For individual ChOOHs, rate constant magnitude (7α/7β-OOH > 5α-OOH > 6α-OOH > 6β-OOH) correlated inversely with reverse-phase HPLC retention time, suggesting that faster transfer reflects greater hydrophilicity. Liposome-borne ChOOHs exhibited the same order of toxicity toward COH-BR1 cells, which are deficient in ability to detoxify these peroxides. The prospect of disseminating oxidative cell injury via translocation of ChOOHs and other lipid hydroperoxides is readily apparent from these findings.</description><subject>Breast Neoplasms - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured - drug effects</subject><subject>Cholesterol - analogs & derivatives</subject><subject>Cholesterol - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Erythrocytes - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Isotope Labeling</subject><subject>Kinetics</subject><subject>Light</subject><subject>Lipid Peroxides - metabolism</subject><subject>Liposomes - metabolism</subject><subject>Models, Chemical</subject><subject>Sterols - chemistry</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0LtO8zAYBmAL_QjKYeAGkJd_YAjYTuIkbKicoYDUwmr58EUY0jiyUw4bK1wmV4JRK1hYbPn1I3_yi9AWJbuUMLqnLKE0I6VfQgOaM5JkVZX_QwNCCE9YxckqWgvhIR4zUmQraJXSgmV5yQfoY9y5tpctuFnAZ20PfgpT5WOAJ3ENNXjsanwnvf0Ww3vXQIjKNckhePsEBp--Gu-6GL1YA3jcgbYQ9j_f3vGFbaG3Go_7mYkZfrb9PR45Aw0eLaYELFuDh9A0YQMt17IJsLnY19Ht8dFkeJpcXp-cDQ8uE5lmVZ_UWvGalrUCzVIwpSlIYZgqZV6wUldADS_LChhTSqYpB06k1lxrXUOm0iJN19HO_F3tXQgeatF5O5X-VVAivvsUP31Guz233UxNwfzKRYERJHNgYysvP_fSPwpepEUuJjdjcXzHrkbnk0xcRf9_7qUO4sHNfBu_-sfgL2nLkHA</recordid><startdate>20011204</startdate><enddate>20011204</enddate><creator>Vila, Andrew</creator><creator>Korytowski, Witold</creator><creator>Girotti, Albert W</creator><general>American Chemical Society</general><scope>BSCLL</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></search><sort><creationdate>20011204</creationdate><title>Spontaneous Intermembrane Transfer of Various Cholesterol-Derived Hydroperoxide Species: Kinetic Studies with Model Membranes and Cells</title><author>Vila, Andrew ; Korytowski, Witold ; Girotti, Albert W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a349t-fcb6f18fbec23ed8d707d2b8a5728c9e1d6889e22bba336e60acc6cccfe4b3733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Breast Neoplasms - metabolism</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured - drug effects</topic><topic>Cholesterol - analogs & derivatives</topic><topic>Cholesterol - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Erythrocytes - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Isotope Labeling</topic><topic>Kinetics</topic><topic>Light</topic><topic>Lipid Peroxides - metabolism</topic><topic>Liposomes - metabolism</topic><topic>Models, Chemical</topic><topic>Sterols - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vila, Andrew</creatorcontrib><creatorcontrib>Korytowski, Witold</creatorcontrib><creatorcontrib>Girotti, Albert W</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vila, Andrew</au><au>Korytowski, Witold</au><au>Girotti, Albert W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spontaneous Intermembrane Transfer of Various Cholesterol-Derived Hydroperoxide Species: Kinetic Studies with Model Membranes and Cells</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>2001-12-04</date><risdate>2001</risdate><volume>40</volume><issue>48</issue><spage>14715</spage><epage>14726</epage><pages>14715-14726</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>Whereas spontaneous and protein-mediated transfer/exchange of cholesterol (Ch) between membranes has been widely studied, relatively little is known about the translocation of Ch oxidation products, particularly hydroperoxide species (ChOOHs), which can act as cytotoxic prooxidants. A major aim of the present study was to examine and compare the intermembrane transfer characteristics of several biologically relevant ChOOH isomers, including singlet oxygen-derived 5α-OOH, 6α-OOH, and 6β-OOH and free radical-derived 7α-OOH and 7β-OOH. These species were generated in [14C]Ch-labeled donor membranes [erythrocyte ghosts or unilamellar DMPC/Ch (1.0:0.8 mol/mol) liposomes] by means of dye-sensitized photoperoxidation. Spontaneous transfer to nonoxidized acceptor membranes (DMPC liposomes or ghosts, respectively) at 37 °C was monitored by thin-layer chromatography with phosphorimaging radiodetection (HPTLC-PI) or liquid chromatography with mercury cathode electrochemical detection [HPLC-EC(Hg)]. The former allowed measurement of total (unresolved) ChOOH along with parent Ch, whereas the latter allowed measurement of individual ChOOHs. Ghost membranes in which ∼4% of the Ch had been peroxidized, giving mainly 5α-OOH, transferred total ChOOH and Ch to liposomes in apparent first-order fashion, the rate constant for ChOOH being ∼65 times greater. Like Ch desorption, ChOOH desorption from donor membranes was found to be rate limiting, and rate varied inversely with size when liposomal donors were used. For individual ChOOHs, rate constant magnitude (7α/7β-OOH > 5α-OOH > 6α-OOH > 6β-OOH) correlated inversely with reverse-phase HPLC retention time, suggesting that faster transfer reflects greater hydrophilicity. Liposome-borne ChOOHs exhibited the same order of toxicity toward COH-BR1 cells, which are deficient in ability to detoxify these peroxides. The prospect of disseminating oxidative cell injury via translocation of ChOOHs and other lipid hydroperoxides is readily apparent from these findings.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>11724586</pmid><doi>10.1021/bi011408r</doi><tpages>12</tpages></addata></record> |
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| subjects | Breast Neoplasms - metabolism Cell Membrane - metabolism Cell Survival - drug effects Cells, Cultured - drug effects Cholesterol - analogs & derivatives Cholesterol - metabolism Chromatography, High Pressure Liquid Erythrocytes - metabolism Female Humans Isotope Labeling Kinetics Light Lipid Peroxides - metabolism Liposomes - metabolism Models, Chemical Sterols - chemistry |
| title | Spontaneous Intermembrane Transfer of Various Cholesterol-Derived Hydroperoxide Species: Kinetic Studies with Model Membranes and Cells |
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