A role for metals and free radicals in the induction of apoptosis in thymocytes
Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, b...
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| Veröffentlicht in: | FEBS letters 1994-09, Vol.352 (1), p.58-62 |
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| creator | Wolfe, James T. Ross, David Cohen, Gerald M. |
| description | Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-ϰB. |
| doi_str_mv | 10.1016/0014-5793(94)00920-1 |
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In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-ϰB.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/0014-5793(94)00920-1</identifier><identifier>PMID: 7925943</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Animals ; Antioxidants - pharmacology ; Apoptosis - drug effects ; Apoptosis - physiology ; BHA, butylated hydroxyanisole ; Chelating Agents - pharmacology ; Copper ; Copper - antagonists & inhibitors ; Copper - physiology ; CP-94, 1,2-diethyl-3-hydroxypyridin-4-one ; Detapac, diethylenetriaminepentaacetic acid ; Dexamethasone - pharmacology ; DMPO, 5,5′-dimethyl-1-pyrroline-N-oxide ; DNA - metabolism ; DPDD, N, N′-diphenyl-1,4-phenylenediamine ; Etoposide - pharmacology ; Free radicals ; Free Radicals - antagonists & inhibitors ; Iron - antagonists & inhibitors ; Iron - physiology ; Lymphocytes - cytology ; Lymphocytes - drug effects ; Male ; NF-ϰB ; Nucleosomes - metabolism ; PBN, α-phenyl-tert-butylnitrone ; PDTC, pyrrolidine dithiocarbamate ; Rat ; Rats ; Rats, Inbred F344 ; Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl ; Thymocyte apoptosis ; Thymus Gland - cytology ; Thymus Gland - drug effects</subject><ispartof>FEBS letters, 1994-09, Vol.352 (1), p.58-62</ispartof><rights>1994</rights><rights>FEBS Letters 352 (1994) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5631-ac84d0a59f24f5d797645b1f8f9e0ff52aaf37d198cc517d9757589981a027943</citedby><cites>FETCH-LOGICAL-c5631-ac84d0a59f24f5d797645b1f8f9e0ff52aaf37d198cc517d9757589981a027943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0014-5793(94)00920-1$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7925943$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wolfe, James T.</creatorcontrib><creatorcontrib>Ross, David</creatorcontrib><creatorcontrib>Cohen, Gerald M.</creatorcontrib><title>A role for metals and free radicals in the induction of apoptosis in thymocytes</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-ϰB.</description><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>BHA, butylated hydroxyanisole</subject><subject>Chelating Agents - pharmacology</subject><subject>Copper</subject><subject>Copper - antagonists & inhibitors</subject><subject>Copper - physiology</subject><subject>CP-94, 1,2-diethyl-3-hydroxypyridin-4-one</subject><subject>Detapac, diethylenetriaminepentaacetic acid</subject><subject>Dexamethasone - pharmacology</subject><subject>DMPO, 5,5′-dimethyl-1-pyrroline-N-oxide</subject><subject>DNA - metabolism</subject><subject>DPDD, N, N′-diphenyl-1,4-phenylenediamine</subject><subject>Etoposide - pharmacology</subject><subject>Free radicals</subject><subject>Free Radicals - antagonists & inhibitors</subject><subject>Iron - antagonists & inhibitors</subject><subject>Iron - physiology</subject><subject>Lymphocytes - cytology</subject><subject>Lymphocytes - drug effects</subject><subject>Male</subject><subject>NF-ϰB</subject><subject>Nucleosomes - metabolism</subject><subject>PBN, α-phenyl-tert-butylnitrone</subject><subject>PDTC, pyrrolidine dithiocarbamate</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl</subject><subject>Thymocyte apoptosis</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - drug effects</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1OLCEQhYnR6PjzBpqwutFFK3RDA5ubqHHUxMSNrglCETHdzVzo0czbSzsTl1dXFeqcOlV8CB1Tck4JbS8IoaziQjWnip0RompS0S00o1I0VcNauY1m35Y9tJ_zGylvSdUu2hWq5oo1M_R4iVPsAPuYcA-j6TI2g8M-AeBkXLBTJwx4fIVS3NKOIQ44emwWcTHGHDbqqo92NUI-RDu-jMDRph6g5_nN0_Vd9fB4e399-VBZ3ja0MlYyRwxXvmaeO6FEy_gL9dIrIN7z2hjfCEeVtJZT4ZTggkulJDWkFuXyA_RnnbtI8d8S8qj7kC10nRkgLrMWrSgIys9_MtJWylY2k5GtjTbFnBN4vUihN2mlKdETcD3R1BNNrZj-Aq5pGTvZ5C9fenDfQxvCRZ-v9Y_QwepXmXp-c1VPwtRX7Ks7Lfq7DoKC9T1A0tkGGCy4kMCO2sXw_0s_Ab0IoVg</recordid><startdate>19940919</startdate><enddate>19940919</enddate><creator>Wolfe, James T.</creator><creator>Ross, David</creator><creator>Cohen, Gerald M.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19940919</creationdate><title>A role for metals and free radicals in the induction of apoptosis in thymocytes</title><author>Wolfe, James T. ; Ross, David ; Cohen, Gerald M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5631-ac84d0a59f24f5d797645b1f8f9e0ff52aaf37d198cc517d9757589981a027943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>BHA, butylated hydroxyanisole</topic><topic>Chelating Agents - pharmacology</topic><topic>Copper</topic><topic>Copper - antagonists & inhibitors</topic><topic>Copper - physiology</topic><topic>CP-94, 1,2-diethyl-3-hydroxypyridin-4-one</topic><topic>Detapac, diethylenetriaminepentaacetic acid</topic><topic>Dexamethasone - pharmacology</topic><topic>DMPO, 5,5′-dimethyl-1-pyrroline-N-oxide</topic><topic>DNA - metabolism</topic><topic>DPDD, N, N′-diphenyl-1,4-phenylenediamine</topic><topic>Etoposide - pharmacology</topic><topic>Free radicals</topic><topic>Free Radicals - antagonists & inhibitors</topic><topic>Iron - antagonists & inhibitors</topic><topic>Iron - physiology</topic><topic>Lymphocytes - cytology</topic><topic>Lymphocytes - drug effects</topic><topic>Male</topic><topic>NF-ϰB</topic><topic>Nucleosomes - metabolism</topic><topic>PBN, α-phenyl-tert-butylnitrone</topic><topic>PDTC, pyrrolidine dithiocarbamate</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl</topic><topic>Thymocyte apoptosis</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wolfe, James T.</creatorcontrib><creatorcontrib>Ross, David</creatorcontrib><creatorcontrib>Cohen, Gerald M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wolfe, James T.</au><au>Ross, David</au><au>Cohen, Gerald M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A role for metals and free radicals in the induction of apoptosis in thymocytes</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1994-09-19</date><risdate>1994</risdate><volume>352</volume><issue>1</issue><spage>58</spage><epage>62</epage><pages>58-62</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-ϰB.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>7925943</pmid><doi>10.1016/0014-5793(94)00920-1</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antioxidants - pharmacology Apoptosis - drug effects Apoptosis - physiology BHA, butylated hydroxyanisole Chelating Agents - pharmacology Copper Copper - antagonists & inhibitors Copper - physiology CP-94, 1,2-diethyl-3-hydroxypyridin-4-one Detapac, diethylenetriaminepentaacetic acid Dexamethasone - pharmacology DMPO, 5,5′-dimethyl-1-pyrroline-N-oxide DNA - metabolism DPDD, N, N′-diphenyl-1,4-phenylenediamine Etoposide - pharmacology Free radicals Free Radicals - antagonists & inhibitors Iron - antagonists & inhibitors Iron - physiology Lymphocytes - cytology Lymphocytes - drug effects Male NF-ϰB Nucleosomes - metabolism PBN, α-phenyl-tert-butylnitrone PDTC, pyrrolidine dithiocarbamate Rat Rats Rats, Inbred F344 Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl Thymocyte apoptosis Thymus Gland - cytology Thymus Gland - drug effects |
| title | A role for metals and free radicals in the induction of apoptosis in thymocytes |
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