Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells
Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell models. Following previous findings, the objective of this work was to elucidate the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a combination of pharmacological agents and apoptosis-related ass...
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| Veröffentlicht in: | Archives of toxicology 2004-02, Vol.78 (2), p.74-85 |
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| creator | CABADO, A. G LEIRA, F VIEYTES, M. R VIEITES, J. M BOTANA, L. M |
| description | Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell models. Following previous findings, the objective of this work was to elucidate the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a combination of pharmacological agents and apoptosis-related assays. OA-induced apoptosis involves disruption of F-actin cytoskeleton, activation of caspase-3, collapse of mitochondrial membrane potential, DNA fragmentation and decreased levels of monomeric Bcl-2 and Bax proteins. All the agents tested were unable to obliterate changes in F-actin levels, caspase-3 activation or DNA fragmentation, but all of them prevented OA-induced decrease of mitochondrial potential and changes in Bax/Bcl-2 levels. Taken together, these results demonstrate that collapse of mitochondrial membrane potential is accessory in the execution of apoptosis, which is directly dependent on cytoskeletal changes. Mitochondrial changes are mediated by complex associations among the Bcl-2 proteins. Cytochrome c release from mitochondria is a late event, occurring 24 h after OA exposure. Moreover, okadaic acid triggers activation of upstream caspases resembling the extrinsic pathway of apoptosis. |
| doi_str_mv | 10.1007/s00204-003-0505-4 |
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G ; LEIRA, F ; VIEYTES, M. R ; VIEITES, J. M ; BOTANA, L. M</creator><creatorcontrib>CABADO, A. G ; LEIRA, F ; VIEYTES, M. R ; VIEITES, J. M ; BOTANA, L. M</creatorcontrib><description>Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell models. Following previous findings, the objective of this work was to elucidate the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a combination of pharmacological agents and apoptosis-related assays. OA-induced apoptosis involves disruption of F-actin cytoskeleton, activation of caspase-3, collapse of mitochondrial membrane potential, DNA fragmentation and decreased levels of monomeric Bcl-2 and Bax proteins. All the agents tested were unable to obliterate changes in F-actin levels, caspase-3 activation or DNA fragmentation, but all of them prevented OA-induced decrease of mitochondrial potential and changes in Bax/Bcl-2 levels. Taken together, these results demonstrate that collapse of mitochondrial membrane potential is accessory in the execution of apoptosis, which is directly dependent on cytoskeletal changes. Mitochondrial changes are mediated by complex associations among the Bcl-2 proteins. Cytochrome c release from mitochondria is a late event, occurring 24 h after OA exposure. Moreover, okadaic acid triggers activation of upstream caspases resembling the extrinsic pathway of apoptosis.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-003-0505-4</identifier><identifier>PMID: 14652712</identifier><identifier>CODEN: ARTODN</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Actins - drug effects ; Actins - metabolism ; Apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein ; Biological and medical sciences ; Caspase 3 ; Caspases - biosynthesis ; Cell Line, Tumor ; Cells ; Cellular biology ; Cytochromes c - secretion ; Cytoskeleton - drug effects ; Cytoskeleton - metabolism ; DNA Fragmentation ; Dose-Response Relationship, Drug ; Drug Combinations ; Enzyme Inhibitors - toxicity ; Humans ; Medical sciences ; Membrane Potentials - drug effects ; Mitochondria - drug effects ; Mitochondria - enzymology ; Mitochondria - secretion ; Neuroblastoma - drug therapy ; Neuroblastoma - pathology ; Okadaic Acid - toxicity ; Pharmaceutical Preparations ; Proteins ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Toxicology</subject><ispartof>Archives of toxicology, 2004-02, Vol.78 (2), p.74-85</ispartof><rights>2004 INIST-CNRS</rights><rights>Springer-Verlag 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-a85499ecca3bfb229c88df0d9bdd96e02a484d88bb6bc50256fc2df8ead6718e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15939192$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14652712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CABADO, A. G</creatorcontrib><creatorcontrib>LEIRA, F</creatorcontrib><creatorcontrib>VIEYTES, M. R</creatorcontrib><creatorcontrib>VIEITES, J. M</creatorcontrib><creatorcontrib>BOTANA, L. M</creatorcontrib><title>Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><description>Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell models. Following previous findings, the objective of this work was to elucidate the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a combination of pharmacological agents and apoptosis-related assays. OA-induced apoptosis involves disruption of F-actin cytoskeleton, activation of caspase-3, collapse of mitochondrial membrane potential, DNA fragmentation and decreased levels of monomeric Bcl-2 and Bax proteins. All the agents tested were unable to obliterate changes in F-actin levels, caspase-3 activation or DNA fragmentation, but all of them prevented OA-induced decrease of mitochondrial potential and changes in Bax/Bcl-2 levels. Taken together, these results demonstrate that collapse of mitochondrial membrane potential is accessory in the execution of apoptosis, which is directly dependent on cytoskeletal changes. Mitochondrial changes are mediated by complex associations among the Bcl-2 proteins. Cytochrome c release from mitochondria is a late event, occurring 24 h after OA exposure. Moreover, okadaic acid triggers activation of upstream caspases resembling the extrinsic pathway of apoptosis.</description><subject>Actins - drug effects</subject><subject>Actins - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein</subject><subject>Biological and medical sciences</subject><subject>Caspase 3</subject><subject>Caspases - biosynthesis</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Cytochromes c - secretion</subject><subject>Cytoskeleton - drug effects</subject><subject>Cytoskeleton - metabolism</subject><subject>DNA Fragmentation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Combinations</subject><subject>Enzyme Inhibitors - toxicity</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Membrane Potentials - drug effects</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondria - secretion</subject><subject>Neuroblastoma - drug therapy</subject><subject>Neuroblastoma - pathology</subject><subject>Okadaic Acid - toxicity</subject><subject>Pharmaceutical Preparations</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Toxicology</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUuL3DAQhEVIyM5O8gNyCSKQvTlpvWzpGIa8YCGX5CzakrzRjm05knyYf78eZmAhp6bhq6KoIuQdg08MoPtcADjIBkA0oEA18gXZMSl4A53QL8kOhIRGdS27IbelPAIwro14TW6YbBXvGN-R6XCqqRzDGCqO1MeS16XGNNNYaP0b6DGc6ICupry9WGnN8eEh5EJxScum3LA403REj9FRdNE3NQeswdM5rDn1I5aaJqQujGN5Q14NOJbw9nr35M-3r78PP5r7X99_Hr7cN05oVRvUShoTnEPRDz3nxmntB_Cm9960AThKLb3Wfd_2TgFX7eC4H3RA33ZMB7EndxffJad_ayjVTrGcE-Ac0los6ww33dbbnnz4D3xMa563bLYVUumWM7ZB7AK5nErJYbBLjhPmk2Vgz0PYyxB2M7TnIazcNO-vxms_Bf-suDa_AR-vABaH45BxdrE8c8oIwwwXTxCqksA</recordid><startdate>20040201</startdate><enddate>20040201</enddate><creator>CABADO, A. 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G ; LEIRA, F ; VIEYTES, M. R ; VIEITES, J. M ; BOTANA, L. 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G</au><au>LEIRA, F</au><au>VIEYTES, M. R</au><au>VIEITES, J. M</au><au>BOTANA, L. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells</atitle><jtitle>Archives of toxicology</jtitle><addtitle>Arch Toxicol</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>78</volume><issue>2</issue><spage>74</spage><epage>85</epage><pages>74-85</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><coden>ARTODN</coden><abstract>Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell models. Following previous findings, the objective of this work was to elucidate the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a combination of pharmacological agents and apoptosis-related assays. OA-induced apoptosis involves disruption of F-actin cytoskeleton, activation of caspase-3, collapse of mitochondrial membrane potential, DNA fragmentation and decreased levels of monomeric Bcl-2 and Bax proteins. All the agents tested were unable to obliterate changes in F-actin levels, caspase-3 activation or DNA fragmentation, but all of them prevented OA-induced decrease of mitochondrial potential and changes in Bax/Bcl-2 levels. Taken together, these results demonstrate that collapse of mitochondrial membrane potential is accessory in the execution of apoptosis, which is directly dependent on cytoskeletal changes. Mitochondrial changes are mediated by complex associations among the Bcl-2 proteins. Cytochrome c release from mitochondria is a late event, occurring 24 h after OA exposure. Moreover, okadaic acid triggers activation of upstream caspases resembling the extrinsic pathway of apoptosis.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>14652712</pmid><doi>10.1007/s00204-003-0505-4</doi><tpages>12</tpages></addata></record> |
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| subjects | Actins - drug effects Actins - metabolism Apoptosis Apoptosis - drug effects bcl-2-Associated X Protein Biological and medical sciences Caspase 3 Caspases - biosynthesis Cell Line, Tumor Cells Cellular biology Cytochromes c - secretion Cytoskeleton - drug effects Cytoskeleton - metabolism DNA Fragmentation Dose-Response Relationship, Drug Drug Combinations Enzyme Inhibitors - toxicity Humans Medical sciences Membrane Potentials - drug effects Mitochondria - drug effects Mitochondria - enzymology Mitochondria - secretion Neuroblastoma - drug therapy Neuroblastoma - pathology Okadaic Acid - toxicity Pharmaceutical Preparations Proteins Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-bcl-2 - metabolism Toxicology |
| title | Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells |
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