{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:40:19Z","timestamp":1791394819194,"version":"4.3.3"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,7,14]],"date-time":"2011-07-14T00:00:00Z","timestamp":1310601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2011) <jats:bold>118<\/jats:bold>, 855\u2013863.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Tissue plasminogen activator (tPA) is necessary for hippocampal long\u2010term potentiation. Synaptically released zinc also contributes to long\u2010term potentiation, especially in the hippocampal CA3 region. Using cortical cultures, we examined whether zinc increased the concentration and\/or activity of tPA. Two hours after a 10\u2010min exposure to 300\u2003\u03bcM zinc, expression of tPA and its substrate, plasminogen, were significantly increased, as was the proteolytic activity of tPA. In contrast, increasing extracellular or intracellular calcium levels did not affect the expression or secretion of tPA. Changing zinc influx or chelating intracellular zinc also failed to alter tPA\/plasminogen induction by zinc, indicating that zinc acts extracellularly. Zinc\u2010mediated extracellular activation of matrix metalloproteinase (MMP) underlies the up\u2010regulation of brain\u2010derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (Trk) signaling. Consistent with these findings, co\u2010treatment with a neutralizing antibody against BDNF or specific inhibitors of MMPs or Trk largely reversed tPA\/plasminogen induction by zinc. Treatment of cortical cultures with <jats:italic>p<\/jats:italic>\u2010aminophenylmercuric acetate, an MMP activator, MMP\u20102, or BDNF alone induced tPA\/plasminogen expression. BDNF mRNA and protein expression was also increased by zinc and mediated by MMPs. Thus, an extracellular zinc\u2010dependent, MMP\u2010 and BDNF\u2010mediated synaptic mechanism may regulate the levels and activity of tPA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07322.x","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T16:35:31Z","timestamp":1306427731000},"page":"855-863","source":"Crossref","is-referenced-by-count":23,"title":["Zinc\u2010triggered induction of tissue plasminogen activator by brain\u2010derived neurotrophic factor and metalloproteinases"],"prefix":"10.1111","volume":"118","author":[{"given":"Ih\u2010Yeon","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Sun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hak","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Yong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pyung\u2010Lim","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Young","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang\u2010Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/308734a0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(00)00269-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80597-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00238969"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80483-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-12-0832"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-01-00108.1990"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(86)80058-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23004"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2003.11.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61242-X"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000109536"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00334.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/308736a0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.11.026"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403172200"},{"key":"e_1_2_7_18_1","first-page":"443","article-title":"Fibrinolysis\u2013a review","volume":"14","author":"Kane K. K.","year":"1984","journal-title":"Ann. Clin. Lab. Sci."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80378-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.647"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00035-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04417.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"8015","DOI":"10.1523\/JNEUROSCI.21-20-08015.2001","article-title":"Induction of mossy fiber \u2013>; Ca3 long\u2010term potentiation requires translocation of synaptically released Zn2+","volume":"21","author":"Li Y.","year":"2001","journal-title":"J. Neurosci."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20250"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(200011)38:2<187::AID-SYN10>3.0.CO;2-R"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80853-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00834-7"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-05-02003.2000"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/83358"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.03.038"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1100135"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90067-N"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80140-3"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91612-9"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-12-04269.1989"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/361453a0"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90199-P"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116637"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-24-09554.1997"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00014.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm926"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/328640a0"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/349521a0"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1471-4159.2011.07322.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1471-4159.2011.07322.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T11:46:17Z","timestamp":1697370377000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1471-4159.2011.07322.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,14]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1111\/j.1471-4159.2011.07322.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1471-4159.2011.07322.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7,14]]}}}