Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons
Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-thre...
Gespeichert in:
| Veröffentlicht in: | Journal of neurochemistry 1999-11, Vol.73 (5), p.2037-2046 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2046 |
|---|---|
| container_issue | 5 |
| container_start_page | 2037 |
| container_title | Journal of neurochemistry |
| container_volume | 73 |
| creator | MATSUZAKI, H TAMATANI, M MITSUDA, N NAMIKAWA, K KIYAMA, H MIYAKE, S.-I TOHYAMA, M |
| description | Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression. |
| doi_str_mv | 10.1046/j.1471-4159.1999.02037.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17397228</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17397228</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5417-ec5f8422a5f5a83fe9314f3632f91ae51dba2976199e070de6fca66032e1c3513</originalsourceid><addsrcrecordid>eNqNkc9u1DAQxi1ERZfCKyAfELcE_0mc5MBhuyp0odpygLPldcbUS9YOdlKyNx6AA8_Ik5A0q5ZjTx55ft_M6PsQwpSklGTi7S6lWUGTjOZVSquqSgkjvEiHJ2hx33iKFoQwlnCSsVP0PMYdIVRkgj5Dp5TkvCCCL9Dvpe7sreqsd9gbvPze4U_WqQh47W7s1nYRL1vfdj7aiJWr8epGuW8QsXX4XDd_f_1hd9_nasAXQxsgxmnU2tW9hhpvD3hju2A1vh5sDZPqc7B7FQ740rat12rfqgZvoA_exRfoxKgmwsvje4a-vr_4srpMrq4_rFfLq0TnGS0S0LkpM8ZUbnJVcgMVp5nhgjNTUQU5rbeKVYUYnQFSkBqE0UoIwhlQzXPKz9CbeW4b_I8eYif3NmpoGuXA91HSglcFY-UIljOog48xgJHtfL2kRE5JyJ2cDJeT4XJKQt4lIYdR-uq4o9_uof5POFs_Aq-PgIpaNSYop2184BgheZmN2LsZ-2kbODx6v_y4WU0V_wdffaU-</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17397228</pqid></control><display><type>article</type><title>Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons</title><source>Wiley Free Content</source><source>MEDLINE</source><source>IngentaConnect Free/Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>MATSUZAKI, H ; TAMATANI, M ; MITSUDA, N ; NAMIKAWA, K ; KIYAMA, H ; MIYAKE, S.-I ; TOHYAMA, M</creator><creatorcontrib>MATSUZAKI, H ; TAMATANI, M ; MITSUDA, N ; NAMIKAWA, K ; KIYAMA, H ; MIYAKE, S.-I ; TOHYAMA, M</creatorcontrib><description>Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.1999.02037.x</identifier><identifier>PMID: 10537063</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adenoviridae - genetics ; Ageing, cell death ; Akt protein ; Animals ; Apoptosis - drug effects ; bcl-2-Associated X Protein ; Biological and medical sciences ; Caspase 3 ; Caspases - metabolism ; Cell physiology ; Enzyme Activation - drug effects ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; Genetic Vectors ; Hippocampus - cytology ; Insulin-Like Growth Factor I - pharmacology ; Molecular and cellular biology ; Nitric Oxide - pharmacology ; Nitric Oxide Donors - pharmacology ; Nitroprusside - pharmacology ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Journal of neurochemistry, 1999-11, Vol.73 (5), p.2037-2046</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5417-ec5f8422a5f5a83fe9314f3632f91ae51dba2976199e070de6fca66032e1c3513</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.1999.02037.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.1999.02037.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1200584$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10537063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MATSUZAKI, H</creatorcontrib><creatorcontrib>TAMATANI, M</creatorcontrib><creatorcontrib>MITSUDA, N</creatorcontrib><creatorcontrib>NAMIKAWA, K</creatorcontrib><creatorcontrib>KIYAMA, H</creatorcontrib><creatorcontrib>MIYAKE, S.-I</creatorcontrib><creatorcontrib>TOHYAMA, M</creatorcontrib><title>Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.</description><subject>Adenoviridae - genetics</subject><subject>Ageing, cell death</subject><subject>Akt protein</subject><subject>Animals</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 - metabolism</subject><subject>Cell physiology</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>Genetic Vectors</subject><subject>Hippocampus - cytology</subject><subject>Insulin-Like Growth Factor I - pharmacology</subject><subject>Molecular and cellular biology</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi1ERZfCKyAfELcE_0mc5MBhuyp0odpygLPldcbUS9YOdlKyNx6AA8_Ik5A0q5ZjTx55ft_M6PsQwpSklGTi7S6lWUGTjOZVSquqSgkjvEiHJ2hx33iKFoQwlnCSsVP0PMYdIVRkgj5Dp5TkvCCCL9Dvpe7sreqsd9gbvPze4U_WqQh47W7s1nYRL1vfdj7aiJWr8epGuW8QsXX4XDd_f_1hd9_nasAXQxsgxmnU2tW9hhpvD3hju2A1vh5sDZPqc7B7FQ740rat12rfqgZvoA_exRfoxKgmwsvje4a-vr_4srpMrq4_rFfLq0TnGS0S0LkpM8ZUbnJVcgMVp5nhgjNTUQU5rbeKVYUYnQFSkBqE0UoIwhlQzXPKz9CbeW4b_I8eYif3NmpoGuXA91HSglcFY-UIljOog48xgJHtfL2kRE5JyJ2cDJeT4XJKQt4lIYdR-uq4o9_uof5POFs_Aq-PgIpaNSYop2184BgheZmN2LsZ-2kbODx6v_y4WU0V_wdffaU-</recordid><startdate>199911</startdate><enddate>199911</enddate><creator>MATSUZAKI, H</creator><creator>TAMATANI, M</creator><creator>MITSUDA, N</creator><creator>NAMIKAWA, K</creator><creator>KIYAMA, H</creator><creator>MIYAKE, S.-I</creator><creator>TOHYAMA, M</creator><general>Blackwell Science Ltd</general><general>Blackwell</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>7TK</scope></search><sort><creationdate>199911</creationdate><title>Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons</title><author>MATSUZAKI, H ; TAMATANI, M ; MITSUDA, N ; NAMIKAWA, K ; KIYAMA, H ; MIYAKE, S.-I ; TOHYAMA, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5417-ec5f8422a5f5a83fe9314f3632f91ae51dba2976199e070de6fca66032e1c3513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenoviridae - genetics</topic><topic>Ageing, cell death</topic><topic>Akt protein</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein</topic><topic>Biological and medical sciences</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cell physiology</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>Genetic Vectors</topic><topic>Hippocampus - cytology</topic><topic>Insulin-Like Growth Factor I - pharmacology</topic><topic>Molecular and cellular biology</topic><topic>Nitric Oxide - pharmacology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MATSUZAKI, H</creatorcontrib><creatorcontrib>TAMATANI, M</creatorcontrib><creatorcontrib>MITSUDA, N</creatorcontrib><creatorcontrib>NAMIKAWA, K</creatorcontrib><creatorcontrib>KIYAMA, H</creatorcontrib><creatorcontrib>MIYAKE, S.-I</creatorcontrib><creatorcontrib>TOHYAMA, M</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>Neurosciences Abstracts</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MATSUZAKI, H</au><au>TAMATANI, M</au><au>MITSUDA, N</au><au>NAMIKAWA, K</au><au>KIYAMA, H</au><au>MIYAKE, S.-I</au><au>TOHYAMA, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1999-11</date><risdate>1999</risdate><volume>73</volume><issue>5</issue><spage>2037</spage><epage>2046</epage><pages>2037-2046</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>10537063</pmid><doi>10.1046/j.1471-4159.1999.02037.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3042 |
| ispartof | Journal of neurochemistry, 1999-11, Vol.73 (5), p.2037-2046 |
| issn | 0022-3042 1471-4159 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17397228 |
| source | Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Adenoviridae - genetics Ageing, cell death Akt protein Animals Apoptosis - drug effects bcl-2-Associated X Protein Biological and medical sciences Caspase 3 Caspases - metabolism Cell physiology Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Genetic Vectors Hippocampus - cytology Insulin-Like Growth Factor I - pharmacology Molecular and cellular biology Nitric Oxide - pharmacology Nitric Oxide Donors - pharmacology Nitroprusside - pharmacology Phosphatidylinositol 3-Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-bcl-2 - genetics Rats Rats, Sprague-Dawley |
| title | Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl‐2 and Bax Expression Induced by Nitric Oxide in Primary Hippocampal Neurons |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A41%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activation%20of%20Akt%20Kinase%20Inhibits%20Apoptosis%20and%20Changes%20in%20Bcl%E2%80%902%20and%20Bax%20Expression%20Induced%20by%20Nitric%20Oxide%20in%20Primary%20Hippocampal%20Neurons&rft.jtitle=Journal%20of%20neurochemistry&rft.au=MATSUZAKI,%20H&rft.date=1999-11&rft.volume=73&rft.issue=5&rft.spage=2037&rft.epage=2046&rft.pages=2037-2046&rft.issn=0022-3042&rft.eissn=1471-4159&rft.coden=JONRA9&rft_id=info:doi/10.1046/j.1471-4159.1999.02037.x&rft_dat=%3Cproquest_cross%3E17397228%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17397228&rft_id=info:pmid/10537063&rfr_iscdi=true |